3,519 results match your criteria Immunological Reviews [Journal]


The clinical and mechanistic intersection of primary atopic disorders and inborn errors of growth and metabolism.

Immunol Rev 2019 Jan;287(1):135-144

Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.

Dynamic changes in metabolism have long been understood as critical for both the initiation and maintenance of innate and adaptive immune responses. A number of recent advances have clarified details of how metabolic pathways can specifically affect cellular function in immune cells. Critical to this understanding is ongoing study of the congenital disorders of glycosylation and other genetic disorders of metabolism that lead to altered immune function in humans. Read More

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http://dx.doi.org/10.1111/imr.12727DOI Listing
January 2019

Primary immunodeficiencies caused by mutations in actin regulatory proteins.

Immunol Rev 2019 Jan;287(1):121-134

Division of Immunology, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

The identification of patients with monogenic gene defects have illuminated the function of different proteins in the immune system, including proteins that regulate the actin cytoskeleton. Many of these actin regulatory proteins are exclusively expressed in leukocytes and regulate the formation and branching of actin filaments. Their absence or abnormal function leads to defects in immune cell shape, cellular projections, migration, and signaling. Read More

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http://dx.doi.org/10.1111/imr.12716DOI Listing
January 2019
1 Read

Insights into immunity from clinical and basic science studies of DOCK8 immunodeficiency syndrome.

Immunol Rev 2019 Jan;287(1):9-19

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.

DOCK8 immunodeficiency syndrome (DIDS) is a progressive combined immunodeficiency that can be distinguished from other combined immunodeficiencies or hyperimmunoglobulinemia E syndromes in featuring (a) profound susceptibility to virus infections of the skin, with associated skin cancers, and (b) severe food allergies. The DOCK8 locus has many repetitive sequence elements that predispose to the generation of large germline deletions as well as recombination-mediated somatic DNA repair. Residual DOCK8 protein contributes to the variable disease phenotype. Read More

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http://dx.doi.org/10.1111/imr.12723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350515PMC
January 2019
1 Read

Chromosome 22q11.2 deletion syndrome and DiGeorge syndrome.

Immunol Rev 2019 Jan;287(1):186-201

The Children's Hospital of Philadelphia, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.

Chromosome 22q11.2 deletion syndrome is the most common microdeletion syndrome in humans. The effects are protean and highly variable, making a unified approach difficult. Read More

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http://dx.doi.org/10.1111/imr.12701DOI Listing
January 2019
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Introduction: Continuing insights into the healthy and diseased immune system through human genetic investigation.

Immunol Rev 2019 Jan;287(1):5-8

Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.

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http://dx.doi.org/10.1111/imr.12730DOI Listing
January 2019

Common variable immune deficiency: Dissection of the variable.

Immunol Rev 2019 Jan;287(1):145-161

Division of Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, New York.

Starting about 60 years ago, a number of reports appeared that outlined the severe clinical course of a few adult subjects with profound hypogammaglobinemia. Puzzled by the lack of family history and adult onset of symptoms in most, the name "acquired" hypogammaglobinemia was given, but later altered to the current name common variable immune deficiency. Pathology reports remarked on the loss of lymph node architecture and paucity of plasma cells in lymphoid tissues in these subjects. Read More

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http://doi.wiley.com/10.1111/imr.12728
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http://dx.doi.org/10.1111/imr.12728DOI Listing
January 2019
8 Reads

Zero tolerance! A perspective on monogenic disorders with defective regulatory T cells and IBD-like disease.

Immunol Rev 2019 Jan;287(1):236-240

Division of Translational Medicine, Research Branch, Sidra Medicine, Doha, Qatar.

Recently, several studies have investigated a number of rare monogenic autoimmune disorders, in which the causative genetic defects were identified and found to affect the development or function of regulatory T cells (Tregs). The studies of these disorders have facilitated a deeper understanding of the mechanisms involved in immune regulation and tolerance. Furthermore, these studies have highlighted the importance of Tregs in maintaining homeostasis at the mucosal interface between the host and microbiome. Read More

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http://dx.doi.org/10.1111/imr.12717DOI Listing
January 2019

Primary immunodeficiencies reveal the essential role of tissue neutrophils in periodontitis.

Immunol Rev 2019 Jan;287(1):226-235

Oral Immunity and Inflammation Unit, NIDCR, NIH, Bethesda, Maryland.

Periodontitis is a common human inflammatory disease. In this condition, microbiota trigger excessive inflammation in oral mucosal tissues surrounding the dentition, resulting in destruction of tooth-supporting structures (connective tissue and bone). While susceptibility factors for common forms of periodontitis are not clearly understood, studies in patients with single genetic defects reveal a critical role for tissue neutrophils in disease susceptibility. Read More

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http://dx.doi.org/10.1111/imr.12724DOI Listing
January 2019

RAG gene defects at the verge of immunodeficiency and immune dysregulation.

Immunol Rev 2019 Jan;287(1):73-90

Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.

Mutations of the recombinase activating genes (RAG) in humans underlie a broad spectrum of clinical and immunological phenotypes that reflect different degrees of impairment of T- and B-cell development and alterations of mechanisms of central and peripheral tolerance. Recent studies have shown that this phenotypic heterogeneity correlates, albeit imperfectly, with different levels of recombination activity of the mutant RAG proteins. Furthermore, studies in patients and in newly developed animal models carrying hypomorphic RAG mutations have disclosed various mechanisms underlying immune dysregulation in this condition. Read More

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http://dx.doi.org/10.1111/imr.12713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309314PMC
January 2019

FAS and RAS related Apoptosis defects: From autoimmunity to leukemia.

Immunol Rev 2019 Jan;287(1):50-61

Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Paris, France.

The human adaptive immune system recognizes almost all the pathogens that we encounter and all the tumor antigens that may arise during our lifetime. Primary immunodeficiencies affecting lymphocyte development or function therefore lead to severe infections and tumor susceptibility. Furthermore, the fact that autoimmunity is a frequent feature of primary immunodeficiencies reveals a third function of the adaptive immune system: its self-regulation. Read More

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http://dx.doi.org/10.1111/imr.12720DOI Listing
January 2019

Newborn screening for severe combined immunodeficiency and T-cell lymphopenia.

Authors:
Jennifer M Puck

Immunol Rev 2019 Jan;287(1):241-252

Division of Allergy, Immunology and Blood and Marrow Transplantation, Department of Pediatrics, UCSF, San Francisco, California.

The development of a T cell receptor excision circle (TREC) assay utilizing dried blood spots (DBS) made possible universal newborn screening (NBS) for severe combined immunodeficiency (SCID) as a public health measure. Upon being flagged by an abnormal screening test in a SCID screening program, an infant can receive further diagnostic testing for SCID in the neonatal period, prior to onset of infectious complications, to permit immediate institution of protective measures and definitive, life-saving treatment to establish a functional immune system. SCID screening is now the accepted standard of care in state public health departments across the United States, and it is being adopted in many countries. Read More

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http://dx.doi.org/10.1111/imr.12729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324582PMC
January 2019
1 Read

Emerging insights into human health and NK cell biology from the study of NK cell deficiencies.

Immunol Rev 2019 Jan;287(1):202-225

Department of Pediatrics, Columbia University Irving Medical Center, New York, New York.

Human NK cells are innate immune effectors that play a critical roles in the control of viral infection and malignancy. The importance of their homeostasis and function can be demonstrated by the study of patients with primary immunodeficiencies (PIDs), which are part of the family of diseases known as inborn defects of immunity. While NK cells are affected in many PIDs in ways that may contribute to a patient's clinical phenotype, a small number of PIDs have an NK cell abnormality as their major immunological defect. Read More

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http://dx.doi.org/10.1111/imr.12725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310041PMC
January 2019
2 Reads

Lessons from primary immunodeficiencies: Autoimmune regulator and autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.

Immunol Rev 2019 Jan;287(1):103-120

Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.

The discovery of the autoimmune regulator (AIRE) protein and the delineation of its critical contributions in the establishment of central immune tolerance has significantly expanded our understanding of the immunological mechanisms that protect from the development of autoimmune disease. The parallel identification and characterization of patient cohorts with the monogenic disorder autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), which is typically caused by biallelic AIRE mutations, has underscored the critical contribution of AIRE in fungal immune surveillance at mucosal surfaces and in prevention of multiorgan autoimmunity in humans. In this review, we synthesize the current clinical, genetic, molecular and immunological knowledge derived from basic studies in Aire-deficient animals and from APECED patient cohorts. Read More

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http://dx.doi.org/10.1111/imr.12714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309421PMC
January 2019

What did we learn from CTLA-4 insufficiency on the human immune system?

Immunol Rev 2019 Jan;287(1):33-49

Center for Chronic Immunodeficiency (CCI), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Cytotoxic-T-lymphocyte-antigen-4 (CTLA-4) is a negative immune regulator constitutively expressed on regulatory T (Treg) cells and upregulated on activated T cells. CTLA-4 inhibits T cell activation by various suppressive functions including competition with CD28, regulation of the inhibitory function of Treg cells, such as transendocytosis, and the control of adhesion and motility. Intrinsic CTLA-4 signaling has been controversially discussed, but so far no distinct signaling pathway has been identified. Read More

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http://doi.wiley.com/10.1111/imr.12721
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http://dx.doi.org/10.1111/imr.12721DOI Listing
January 2019
12 Reads

WHIM syndrome: Immunopathogenesis, treatment and cure strategies.

Immunol Rev 2019 Jan;287(1):91-102

Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.

WHIM syndrome is a rare, autosomal dominant immunodeficiency which is named for the four key manifestations: Warts, Hypogammaglobulinemia, Infections, and Myelokathexis. It results from heterozygous gain-of-function mutations in the chemokine receptor CXCR4 which is widely expressed on leukocytes and has profound influences on immune system homeostasis and organogenesis. New treatments for the disease using drugs to reduce CXCR4 function are excellent examples of precision medicine. Read More

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http://doi.wiley.com/10.1111/imr.12719
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http://dx.doi.org/10.1111/imr.12719DOI Listing
January 2019
7 Reads

Early-onset inflammatory bowel disease as a model disease to identify key regulators of immune homeostasis mechanisms.

Immunol Rev 2019 Jan;287(1):162-185

Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria.

Rare, monogenetic diseases present unique models to dissect gene functions and biological pathways, concomitantly enhancing our understanding of the etiology of complex (and often more common) traits. Although inflammatory bowel disease (IBD) is a generally prototypic complex disease, it can also manifest in an early-onset, monogenic fashion, often following Mendelian modes of inheritance. Recent advances in genomic technologies have spurred the identification of genetic defects underlying rare, very early-onset IBD (VEO-IBD) as a disease subgroup driven by strong genetic influence, pinpointing key players in the delicate homeostasis of the immune system in the gut and illustrating the intimate relationships between bowel inflammation, systemic immune dysregulation, and primary immunodeficiency with increased susceptibility to infections. Read More

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http://doi.wiley.com/10.1111/imr.12726
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http://dx.doi.org/10.1111/imr.12726DOI Listing
January 2019
9 Reads

CHAPLE syndrome uncovers the primary role of complement in a familial form of Waldmann's disease.

Authors:
Ahmet Ozen

Immunol Rev 2019 Jan;287(1):20-32

Division of Allergy and Immunology, Marmara University School of Medicine, Istanbul, Turkey.

Primary intestinal lymphangiectasia (PIL) or Waldmann's disease was described in 1961 as an important cause of protein-losing enteropathy (PLE). PIL can be the sole finding in rare individuals or occur as part of a multisystemic genetic syndrome. Although genetic etiologies of many lymphatic dysplasia syndromes associated with PIL have been identified, the pathogenesis of isolated PIL (with no associated syndromic features) remains unknown. Read More

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http://dx.doi.org/10.1111/imr.12715DOI Listing
January 2019
1 Read

Human adenosine deaminase 2 deficiency: A multi-faceted inborn error of immunity.

Immunol Rev 2019 Jan;287(1):62-72

Department of Microbiology and Immunology, Laboratory for Childhood Immunology, KU Leuven, Leuven, Belgium.

Human adenosine deaminase 1 deficiency was described in the 1970s to cause severe combined immunodeficiency. The residual adenosine deaminase activity in these patients was attributed to adenosine deaminase 2. Human adenosine deaminase type 2 deficiency (DADA2), due to biallelic deleterious mutations in the ADA2 gene, is the first described monogenic type of small- and medium-size vessel vasculitis. Read More

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http://dx.doi.org/10.1111/imr.12722DOI Listing
January 2019
6 Reads

Metabolic regulation of innate and adaptive lymphocyte effector responses.

Immunol Rev 2018 11;286(1):137-147

Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology, Weill Cornell Medicine, New York, New York.

Innate and adaptive lymphocytes employ diverse effector programs that provide optimal immunity to pathogens and orchestrate tissue homeostasis, or conversely can become dysregulated to drive progression of chronic inflammatory diseases. Emerging evidence suggests that CD4 T helper cell subsets and their innate counterparts, the innate lymphoid cell family, accomplish these complex biological roles by selectively programming their cellular metabolism in order to instruct distinct modules of lymphocyte differentiation, proliferation, and cytokine production. Further, these metabolic pathways are significantly influenced by tissue microenvironments and disease states. Read More

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http://doi.wiley.com/10.1111/imr.12703
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http://dx.doi.org/10.1111/imr.12703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195227PMC
November 2018
1 Read

Spatial and temporal coordination of antiviral responses by group 1 ILCs.

Immunol Rev 2018 11;286(1):23-36

Immunology Program, Memorial Sloan Kettering Cancer Center, New York.

Group 1 innate lymphocytes consist of a phenotypically, spatially, and functionally heterogeneous population of NK cells and ILC1s that are engaged during pathogen invasion. We are only beginning to understand the context-dependent roles that different subsets of group 1 innate lymphocytes play during homeostatic perturbations. With a focus on viral infection, this review highlights the organization and regulation of spatially and temporally distinct waves of NK cell and ILC1 responses that collectively serve to achieve optimal viral control. Read More

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http://doi.wiley.com/10.1111/imr.12710
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http://dx.doi.org/10.1111/imr.12710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178831PMC
November 2018
13 Reads

New insights into the function, development, and plasticity of type 2 innate lymphoid cells.

Immunol Rev 2018 11;286(1):74-85

Department of Experimental Immunology, Amsterdam-UMC, Amsterdam, the Netherlands.

Group 2 innate lymphoid cells (ILC2s) are the most well defined group of ILCs. ILC2 development is controlled by the GATA-3 transcription factor and these cells produce archetypal type 2 cytokines, such as IL-5 and IL-13. These cytokines mediate parasite expulsion and tissue repair, but also contribute to type 2 inflammatory diseases, including allergy, asthma and chronic rhinosinusitis with nasal polyps. Read More

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http://dx.doi.org/10.1111/imr.12708DOI Listing
November 2018

Thinking differently about ILCs-Not just tissue resident and not just the same as CD4 T-cell effectors.

Immunol Rev 2018 11;286(1):160-171

Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National institute of Health, Bethesda, Maryland.

Innate lymphoid cells (ILCs) resemble adaptive T lymphocytes based on transcription factor expression, cytokine production, and their presumptive roles in immunity, but are activated for effector function through cytokine signaling and not antigen-specific receptors. The prevailing view is that ILCs adapt to specific microenvironments during development and operate as tissue-resident cells in co-operation with antigen-specific T cells to provide host protection and contribute to tissue maintenance. In particular, conventional models equate the activity of different ILC subsets with CD4 effector T-cell types based on corresponding transcription factor expression and a potential for comparable cytokine production. Read More

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http://doi.wiley.com/10.1111/imr.12704
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http://dx.doi.org/10.1111/imr.12704DOI Listing
November 2018
10 Reads

Introduction: Basic and emerging concepts in ILC biology.

Authors:
Marco Colonna

Immunol Rev 2018 11;286(1):4-5

Washington University School of Medicine, St Louis, Missouri.

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http://doi.wiley.com/10.1111/imr.12711
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http://dx.doi.org/10.1111/imr.12711DOI Listing
November 2018
2 Reads

Deconstructing deployment of the innate immune lymphocyte army for barrier homeostasis and protection.

Immunol Rev 2018 11;286(1):6-22

Division of Molecular Immunology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.

The study of the immune system has shifted from a purely dichotomous separation between the innate and adaptive arms to one that is now highly complex and reshaping our ideas of how steady-state health is assured. It is now clear that immune cells do not neatly fit into these two streams and immune homeostasis depends on continual dialogue between multiple lineages of the innate (including dendritic cells, innate lymphoid cells, and unconventional lymphocytes) and adaptive (T and B lymphocytes) arms together with a finely tuned synergy between the host and microbes which is essential to ensure immune homeostasis. Innate lymphoid cells are critical players in this new landscape. Read More

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http://dx.doi.org/10.1111/imr.12709DOI Listing
November 2018

JAK/STAT signaling in regulation of innate lymphoid cells: The gods before the guardians.

Immunol Rev 2018 11;286(1):148-159

Department of Molecular Medicine, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy.

Immunity to pathogens is ensured through integration of early responses mediated by innate cells and late effector functions taking place after terminal differentiation of adaptive lymphocytes. In this context, innate lymphoid cells (ILCs) and adaptive T cells represent a clear example of how prototypical effector functions, including polarized expression of cytokines and/or cytotoxic activity, can occur with overlapping modalities but different timing. The ability of ILCs to provide early protection relies on their poised epigenetic state, which determines their propensity to quickly respond to cytokines and to activate specific patterns of signal-dependent transcription factors. Read More

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http://dx.doi.org/10.1111/imr.12705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178832PMC
November 2018
1 Read

Innate lymphoid cells in lung infection and immunity.

Immunol Rev 2018 11;286(1):102-119

Innate Immunity, Deutsches Rheuma-Forschungszentrum, Berlin, Germany.

In recent years, innate lymphoid cells (ILCs) have emerged as key mediators of protection and repair of mucosal surfaces during infection. The lung, a dynamic mucosal tissue that is exposed to a plethora of microbes, is a playground for respiratory infection-causing pathogens which are not only a major cause of fatalities worldwide, but are also associated with comorbidities and decreased quality of life. The lung provides a rich microenvironment to study ILCs in the context of innate protection mechanisms within the airways, unraveling their distinct functions not only in health but also in disease. Read More

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http://doi.wiley.com/10.1111/imr.12712
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http://dx.doi.org/10.1111/imr.12712DOI Listing
November 2018
17 Reads

The group 2 innate lymphoid cell (ILC2) regulatory network and its underlying mechanisms.

Immunol Rev 2018 11;286(1):37-52

Laboratory for Immune Cell Systems, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan.

Group 2 innate lymphoid cells (ILC2s) play critical roles in the induction of type 2 inflammation, response to parasite infection, metabolic homeostasis, and tissue repair. These multifunctional roles of ILC2s are tightly controlled by complex regulatory systems in the local microenvironment, the disruption of which may cause various health problems. This review summarizes up-to-date knowledge regarding positive and negative regulators for ILC2s based on their function and signaling pathways, including activating cytokines (IL-33, IL-25; MAPK, NF-κB pathways), co-stimulatory cytokines (IL-2, IL-7, IL-9, TSLP; STAT5, IL-4; STAT6, TNF superfamily; MAPK, NF-κB pathways), suppressive cytokines (type1 IFNs, IFN-γ, IL-27; STAT1, IL-10, TGF-β), transdifferentiation cytokines (IL-12; STAT4, IL-1β, IL-18), lipid mediators (LTC4, LTD4, LTE4, PGD2; Ca -NFAT pathways, PGE2, PGI2; AC/cAMP/PKA pathways, LXA4, LTB4), neuropeptides (NMU; Ca -NFAT, MAPK pathways, VIP, CGRP, catecholamine, acetylcholine), sex hormones (androgen, estrogen), nutrients (butyrate; HDAC inhibitors, vitamins), and cell-to-cell interactions (ICOSL-ICOS; STAT5, B7-H6-NKp30, E-cadherin-KLRG1). Read More

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http://doi.wiley.com/10.1111/imr.12706
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http://dx.doi.org/10.1111/imr.12706DOI Listing
November 2018
3 Reads

Type 2 innate lymphoid cells in the induction and resolution of tissue inflammation.

Immunol Rev 2018 11;286(1):53-73

Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham & Women's Hospital, Boston, Massachusetts.

Type 2 immunity against pathogens is tightly regulated to ensure appropriate inflammatory responses that clear infection and prevent excessive tissue damage. Recent research has shown that type 2 innate lymphoid cells (ILC2s) contribute to steady-state tissue integrity and exert tissue-specific functions. However, upon exposure to inflammatory stimuli, they also initiate and amplify type 2 inflammation by inducing mucus production, eosinophilia, and Th2 differentiation. Read More

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http://dx.doi.org/10.1111/imr.12702DOI Listing
November 2018
4 Reads

Innate lymphoid cells, mediators of tissue homeostasis, adaptation and disease tolerance.

Immunol Rev 2018 11;286(1):86-101

Laboratory of Innate Immunity, Department of Microbiology, Infectious Diseases and Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Innate lymphoid cells (ILC) are a recently identified group of tissue-resident innate lymphocytes. Available data support the view that ILC or their progenitors are deposited and retained in tissues early during ontogeny. Thereby, ILC become an integral cellular component of tissues and organs. Read More

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http://dx.doi.org/10.1111/imr.12718DOI Listing
November 2018

Neuroendocrine regulation of innate lymphoid cells.

Immunol Rev 2018 11;286(1):120-136

Aix Marseille Univ, CNRS, INSERM, CIML, Centre d'Immunologie de Marseille-Luminy, Marseille, France.

The activities of the immune system in repairing tissue injury and combating pathogens were long thought to be independent of the nervous system. However, a major regulatory role of immunomodulatory molecules released locally or systemically by the neuroendocrine system has recently emerged. A number of observations and discoveries support indeed the notion of the nervous system as an immunoregulatory system involved in immune responses. Read More

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http://doi.wiley.com/10.1111/imr.12707
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http://dx.doi.org/10.1111/imr.12707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221181PMC
November 2018
1 Read

Dynamic balance of pro- and anti-inflammatory signals controls disease and limits pathology.

Immunol Rev 2018 09;285(1):147-167

Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA.

Immune responses to pathogens are complex and not well understood in many diseases, and this is especially true for infections by persistent pathogens. One mechanism that allows for long-term control of infection while also preventing an over-zealous inflammatory response from causing extensive tissue damage is for the immune system to balance pro- and anti-inflammatory cells and signals. This balance is dynamic and the immune system responds to cues from both host and pathogen, maintaining a steady state across multiple scales through continuous feedback. Read More

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http://dx.doi.org/10.1111/imr.12671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292442PMC
September 2018
10.120 Impact Factor

Insight into treatment of HIV infection from viral dynamics models.

Immunol Rev 2018 09;285(1):9-25

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

The odds of living a long and healthy life with HIV infection have dramatically improved with the advent of combination antiretroviral therapy. Along with the early development and clinical trials of these drugs, and new field of research emerged called viral dynamics, which uses mathematical models to interpret and predict the time-course of viral levels during infection and how they are altered by treatment. In this review, we summarize the contributions that virus dynamics models have made to understanding the pathophysiology of infection and to designing effective therapies. Read More

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http://dx.doi.org/10.1111/imr.12698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155466PMC
September 2018
13 Reads

Mathematical modeling of within-host Zika virus dynamics.

Immunol Rev 2018 09;285(1):81-96

Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA.

Recent Zika virus outbreaks have been associated with severe outcomes, especially during pregnancy. A great deal of effort has been put toward understanding this virus, particularly the immune mechanisms responsible for rapid viral control in the majority of infections. Identifying and understanding the key mechanisms of immune control will provide the foundation for the development of effective vaccines and antiviral therapy. Read More

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http://doi.wiley.com/10.1111/imr.12687
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http://dx.doi.org/10.1111/imr.12687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107313PMC
September 2018
14 Reads

The natural history of naive T cells from birth to maturity.

Immunol Rev 2018 09;285(1):218-232

Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York.

Generating and maintaining a diverse repertoire of naive T cells is essential for protection against pathogens, and developing a mechanistic and quantitative description of the processes involved lies at the heart of our understanding of vertebrate immunity. Here, we review the biology of naive T cells from birth to maturity and outline how the integration of mathematical models and experiments has helped us to develop a full picture of their life histories. Read More

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http://dx.doi.org/10.1111/imr.12694DOI Listing
September 2018
1 Read

Herpes simplex virus-2 dynamics as a probe to measure the extremely rapid and spatially localized tissue-resident T-cell response.

Immunol Rev 2018 09;285(1):113-133

Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Herpes simplex virus-2 infection is characterized by frequent episodic shedding in the genital tract. Expansion in HSV-2 viral load early during episodes is extremely rapid. However, the virus invariably peaks within 18 hours and is eliminated nearly as quickly. Read More

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http://dx.doi.org/10.1111/imr.12672DOI Listing
September 2018
10 Reads

Molecular mechanisms of T cell sensitivity to antigen.

Immunol Rev 2018 09;285(1):194-205

Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.

T cells initiate and regulate adaptive immune responses that can clear infections. To do this, they use their T cell receptors (TCRs) to continually scan the surfaces of other cells for cognate peptide antigens presented on major histocompatibility complexes (pMHCs). Experimental work has established that as few 1-10 pMHCs are sufficient to activate T cells. Read More

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http://dx.doi.org/10.1111/imr.12690DOI Listing
September 2018

Antiviral interferon response at single-cell resolution.

Immunol Rev 2018 09;285(1):72-80

Division of Theoretical Systems Biology, German Cancer Research Center (DKFZ) and Bioquant Center, University of Heidelberg, Heidelberg, Germany.

Experimental studies of the innate immune response of mammalian cells to viruses reveal pervasive heterogeneity at the level of single cells. Interferons are induced only in a fraction of virus-infected cells; subsequently a fraction of cells exposed to interferons upregulate interferon-stimulated genes. Nevertheless, quantitative experiments and linked mathematical models show that the interferon response can be effective in curbing viral spread through two distinct mechanisms. Read More

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http://dx.doi.org/10.1111/imr.12699DOI Listing
September 2018

Virus dynamics and phyloanatomy: Merging population dynamic and phylogenetic approaches.

Immunol Rev 2018 09;285(1):134-146

Institute of Integrative Biology, ETH Zurich, Zurich, Switzerland.

In evolutionary biology and epidemiology, phylodynamic methods are widely used to infer population biological characteristics, such as the rates of replication, death, migration, or, in the epidemiological context, pathogen spread. More recently, these methods have been used to elucidate the dynamics of viruses within their hosts. Especially the application of phylogeographic approaches has the potential to shed light on anatomical colonization pathways and the exchange of viruses between distinct anatomical compartments. Read More

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http://doi.wiley.com/10.1111/imr.12688
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http://dx.doi.org/10.1111/imr.12688DOI Listing
September 2018
14 Reads

Modifying clonal selection theory with a probabilistic cell.

Authors:
Philip D Hodgkin

Immunol Rev 2018 09;285(1):249-262

Immunology Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, Vic., Australia.

Problem-solving strategies in immunology currently utilize a series of ad hoc, qualitative variations on a foundation of Burnet's formulation of clonal selection theory. These modifications, including versions of two-signal theory, describe how signals regulate lymphocytes to make important decisions governing self-tolerance and changes to their effector and memory states. These theories are useful but are proving inadequate to explain the observable genesis and control of heterogeneity in cell types, the nonlinear passage of cell fate trajectories and how the input from multiple environmental signals can be integrated at different times and strengths. Read More

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http://dx.doi.org/10.1111/imr.12695DOI Listing
September 2018

The dynamics of simian immunodeficiency virus after depletion of CD8+ cells.

Immunol Rev 2018 09;285(1):26-37

Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico.

Human immunodeficiency virus infection is still one of the most important causes of morbidity and mortality in the world, with a disproportionate human and economic burden especially in poorer countries. Despite many years of intense research, an aspect that still is not well understood is what (immune) mechanisms control the viral load during the prolonged asymptomatic stage of infection. Because CD8+ T cells have been implicated in this control by multiple lines of evidence, there has been a focus on understanding the potential mechanisms of action of this immune effector population. Read More

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http://doi.wiley.com/10.1111/imr.12691
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http://dx.doi.org/10.1111/imr.12691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352983PMC
September 2018
16 Reads

Interferon at the cellular, individual, and population level in hepatitis C virus infection: Its role in the interferon-free treatment era.

Immunol Rev 2018 09;285(1):55-71

Department of Chemical Engineering, Indian Institute of Science, Bangalore, India.

The advent of powerful direct-acting antiviral agents (DAAs) has revolutionized the treatment of hepatitis C. DAAs cure nearly all patients with short duration, oral treatments. Significant efforts are now underway to optimize DAA-based treatments. Read More

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http://dx.doi.org/10.1111/imr.12689DOI Listing
September 2018
15 Reads

Some deterministic and stochastic mathematical models of naïve T-cell homeostasis.

Immunol Rev 2018 09;285(1):206-217

School of Mathematics, University of Leeds, Leeds, UK.

Humans live for decades, whereas mice live for months. Over these long timescales, naïve T cells die or divide infrequently enough that it makes sense to approximate death and division as instantaneous events. The population of T cells in the body is naturally divided into clonotypes; a clonotype is the set of cells that have identical T-cell receptors. Read More

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http://dx.doi.org/10.1111/imr.12696DOI Listing
September 2018
1 Read

Host-pathogen kinetics during influenza infection and coinfection: insights from predictive modeling.

Authors:
Amber M Smith

Immunol Rev 2018 09;285(1):97-112

University of Tennessee Health Science Center, Memphis, TN, USA.

Influenza virus infections are a leading cause of morbidity and mortality worldwide. This is due in part to the continual emergence of new viral variants and to synergistic interactions with other viruses and bacteria. There is a lack of understanding about how host responses work to control the infection and how other pathogens capitalize on the altered immune state. Read More

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http://doi.wiley.com/10.1111/imr.12692
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http://dx.doi.org/10.1111/imr.12692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175135PMC
September 2018
2 Reads

Introduction to modeling viral infections and immunity.

Immunol Rev 2018 09;285(1):5-8

Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM, USA.

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http://dx.doi.org/10.1111/imr.12700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312192PMC
September 2018
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Within-host modeling of blood-stage malaria.

Immunol Rev 2018 09;285(1):168-193

Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.

Malaria infection continues to be a major health problem worldwide and drug resistance in the major human parasite species, Plasmodium falciparum, is increasing in South East Asia. Control measures including novel drugs and vaccines are in development, and contributions to the rational design and optimal usage of these interventions are urgently needed. Infection involves the complex interaction of parasite dynamics, host immunity, and drug effects. Read More

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http://doi.wiley.com/10.1111/imr.12697
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http://dx.doi.org/10.1111/imr.12697DOI Listing
September 2018
51 Reads

Modeling the dynamics of hepatitis B infection, immunity, and drug therapy.

Authors:
Stanca M Ciupe

Immunol Rev 2018 09;285(1):38-54

Department of Mathematics, Virginia Tech, Blacksburg, VA, USA.

Hepatitis B virus infection is the cause of liver diseases such as cirrhosis and liver cancer. Understanding the host-virus mechanisms that mediate virus pathogenesis can help design better preventive measures for disease control. Mathematical models have been used alongside experimental data to provide insight into the role of immune responses during the acute and chronic hepatitis B infections as well as virus dynamics following administration of combined drug therapy. Read More

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http://doi.wiley.com/10.1111/imr.12686
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http://dx.doi.org/10.1111/imr.12686DOI Listing
September 2018
12 Reads

Current best estimates for the average lifespans of mouse and human leukocytes: reviewing two decades of deuterium-labeling experiments.

Immunol Rev 2018 09;285(1):233-248

Theoretical Biology & Bioinformatics, Utrecht, The Netherlands.

Deuterium is a non-toxic, stable isotope that can safely be administered to humans and mice to study their cellular turnover rates in vivo. It is incorporated into newly synthesized DNA strands during cell division, without interference with the kinetics of cells, and the accumulation and loss of deuterium in the DNA of sorted (sub-)populations of leukocytes can be used to estimate their cellular production rates and lifespans. In the past two decades, this powerful technology has been used to estimate the turnover rates of various types of leukocytes. Read More

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http://dx.doi.org/10.1111/imr.12693DOI Listing
September 2018

CD4 T cells in protection from influenza virus: Viral antigen specificity and functional potential.

Immunol Rev 2018 07;284(1):91-105

David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA.

CD4 T cells convey a number of discrete functions to protective immunity to influenza, a complexity that distinguishes this arm of adaptive immunity from B cells and CD8 T cells. Although the most well recognized function of CD4 T cells is provision of help for antibody production, CD4 T cells are important in many aspects of protective immunity. Our studies have revealed that viral antigen specificity is a key determinant of CD4 T cell function, as illustrated both by mouse models of infection and human vaccine responses, a factor whose importance is due at least in part to events in viral antigen handling. Read More

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http://dx.doi.org/10.1111/imr.12662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070306PMC
July 2018
2 Reads

Human adaptive immune receptor repertoire analysis-Past, present, and future.

Immunol Rev 2018 07;284(1):9-23

Department of Pathology, Stanford University, Stanford, CA, USA.

The genes encoding adaptive immune antigen receptors, namely the immunoglobulins expressed in membrane-bound or secreted forms by B cells, and the cell surface T cell receptors, are unique in human biology because they are generated by combinatorial rearrangement of the genomic DNA. The diversity of receptors so generated in populations of lymphocytes enables the human immune system to recognize antigens expressed by pathogens, but also underlies the pathological specificity of autoimmune diseases and the mistargeted immunity in allergies. Several recent technological developments, foremost among them the invention of high-throughput DNA sequencing instruments, have enabled much deeper and thorough evaluation of clones of human B cells and T cells and the antigen receptors they express during physiological and pathogenic immune responses. Read More

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http://dx.doi.org/10.1111/imr.12667DOI Listing
July 2018
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Characterization of the immunologic repertoire: A quick start guide.

Immunol Rev 2018 07;284(1):5-8

Department of Ecology & Evolution, The Committee on Microbiology, The University of Chicago, Chicago, IL, USA.

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http://dx.doi.org/10.1111/imr.12685DOI Listing
July 2018
1 Read