Publications by authors named "Sachin P Gadani"

11 Publications

  • Page 1 of 1

Granulomatosis with Polyangiitis Manifesting as a Symptomatic Sellar Mass in a Young Woman.

Cureus 2019 Oct 2;11(10):e5823. Epub 2019 Oct 2.

Pulmonary and Critical Care, University of Maryland, Baltimore, USA.

A pituitary mass is a rare and poorly understood complication of granulomatosis with polyangiitis (GPA). Here we describe the case of a young woman with GPA who presented with signs and symptoms initially suggestive of meningitis but was ultimately found to have hypopituitarism and an enlarging sellar mass. She underwent transsphenoidal biopsy, which revealed an abundance of sterile inflammation and necrosis consistent with GPA-related inflammation. This case demonstrates a rare complication of GPA, i.e., a pituitary mass, initially mimicking meningitis. GPA-related pituitary involvement has an unknown pathogenesis and can have debilitating long-term consequences including chronic hypopituitarism and vision impairment, highlighting the need for further research.
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http://dx.doi.org/10.7759/cureus.5823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827696PMC
October 2019

How and why do T cells and their derived cytokines affect the injured and healthy brain?

Nat Rev Neurosci 2017 06 27;18(6):375-384. Epub 2017 Apr 27.

Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.

The evolution of adaptive immunity provides enhanced defence against specific pathogens, as well as homeostatic immune surveillance of all tissues. Despite being 'immune privileged', the CNS uses the assistance of the immune system in physiological and pathological states. In this Opinion article, we discuss the influence of adaptive immunity on recovery after CNS injury and on cognitive and social brain function. We further extend a hypothesis that the pro-social effects of interferon-regulated genes were initially exploited by pathogens to increase host-host transmission, and that these genes were later recycled by the host to form part of an immune defence programme. In this way, the evolution of adaptive immunity may reflect a host-pathogen 'arms race'.
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http://dx.doi.org/10.1038/nrn.2017.39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823005PMC
June 2017

Characterization of meningeal type 2 innate lymphocytes and their response to CNS injury.

J Exp Med 2017 02 19;214(2):285-296. Epub 2016 Dec 19.

Center for Brain Immunology and Glia (BIG), University of Virginia, Charlottesville, VA 22908

The meningeal space is occupied by a diverse repertoire of immune cells. Central nervous system (CNS) injury elicits a rapid immune response that affects neuronal survival and recovery, but the role of meningeal inflammation remains poorly understood. Here, we describe type 2 innate lymphocytes (ILC2s) as a novel cell type resident in the healthy meninges that are activated after CNS injury. ILC2s are present throughout the naive mouse meninges, though are concentrated around the dural sinuses, and have a unique transcriptional profile. After spinal cord injury (SCI), meningeal ILC2s are activated in an IL-33-dependent manner, producing type 2 cytokines. Using RNAseq, we characterized the gene programs that underlie the ILC2 activation state. Finally, addition of wild-type lung-derived ILC2s into the meningeal space of IL-33R animals partially improves recovery after SCI. These data characterize ILC2s as a novel meningeal cell type that responds to SCI and could lead to new therapeutic insights for neuroinflammatory conditions.
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http://dx.doi.org/10.1084/jem.20161982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294864PMC
February 2017

Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour.

Nature 2016 07 13;535(7612):425-9. Epub 2016 Jul 13.

Immune dysfunction is commonly associated with several neurological and mental disorders. Although the mechanisms by which peripheral immunity may influence neuronal function are largely unknown, recent findings implicate meningeal immunity influencing behaviour, such as spatial learning and memory. Here we show that meningeal immunity is also critical for social behaviour; mice deficient in adaptive immunity exhibit social deficits and hyper-connectivity of fronto-cortical brain regions. Associations between rodent transcriptomes from brain and cellular transcriptomes in response to T-cell-derived cytokines suggest a strong interaction between social behaviour and interferon-γ (IFN-γ)-driven responses. Concordantly, we demonstrate that inhibitory neurons respond to IFN-γ and increase GABAergic (γ-aminobutyric-acid) currents in projection neurons, suggesting that IFN-γ is a molecular link between meningeal immunity and neural circuits recruited for social behaviour. Meta-analysis of the transcriptomes of a range of organisms reveals that rodents, fish, and flies elevate IFN-γ/JAK-STAT-dependent gene signatures in a social context, suggesting that the IFN-γ signalling pathway could mediate a co-evolutionary link between social/aggregation behaviour and an efficient anti-pathogen response. This study implicates adaptive immune dysfunction, in particular IFN-γ, in disorders characterized by social dysfunction and suggests a co-evolutionary link between social behaviour and an anti-pathogen immune response driven by IFN-γ signalling.
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http://dx.doi.org/10.1038/nature18626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961620PMC
July 2016

Shedding light on IL-33 in the eye.

J Exp Med 2016 Feb;213(2):141

Center for Brain Immunology and Glia, Department of Neuroscience, Graduate Program in Neuroscience and Medical Scientist Training Program, School of Medicine, University of Virginia

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http://dx.doi.org/10.1084/jem.2132insight2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749930PMC
February 2016

Natural killers in the brain's nursery.

Nat Neurosci 2016 Feb;19(2):176-7

Center for Brain Immunology and Glia, Department of Neuroscience, Graduate Program in Neuroscience and Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.

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http://dx.doi.org/10.1038/nn.4227DOI Listing
February 2016

Dealing with Danger in the CNS: The Response of the Immune System to Injury.

Neuron 2015 Jul;87(1):47-62

Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA; Graduate Program in Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA; Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA. Electronic address:

Fighting pathogens and maintaining tissue homeostasis are prerequisites for survival. Both of these functions are upheld by the immune system, though the latter is often overlooked in the context of the CNS. The mere presence of immune cells in the CNS was long considered a hallmark of pathology, but this view has been recently challenged by studies demonstrating that immunological signaling can confer pivotal neuroprotective effects on the injured CNS. In this review, we describe the temporal sequence of immunological events that follow CNS injury. Beginning with immediate changes at the injury site, including death of neural cells and release of damage-associated molecular patterns (DAMPs), and progressing through innate and adaptive immune responses, we describe the cascade of inflammatory mediators and the implications of their post-injury effects. We conclude by proposing a revised interpretation of immune privilege in the brain, which takes beneficial neuro-immune communications into account.
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http://dx.doi.org/10.1016/j.neuron.2015.05.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491143PMC
July 2015

Brainless immunity no more.

Nat Immunol 2015 May;16(5):440-1

Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, Virginia, USA.

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http://dx.doi.org/10.1038/ni.3145DOI Listing
May 2015

The glia-derived alarmin IL-33 orchestrates the immune response and promotes recovery following CNS injury.

Neuron 2015 Feb 5;85(4):703-9. Epub 2015 Feb 5.

Center for Brain Immunology and Glia, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA; Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA; Graduate Program in Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA; Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA. Electronic address:

Inflammation is a prominent feature of CNS injury that heavily influences neuronal survival, yet the signals that initiate and control it remain poorly understood. Here we identify the nuclear alarmin, interleukin (IL)-33, as an important regulator of the innate immune response after CNS injury. IL-33 is expressed widely throughout the healthy brain and is concentrated in white mater due to predominant expression in post-mitotic oligodendrocytes. IL-33 is released immediately after CNS injury from damaged oligodendrocytes, acting on local astrocytes and microglia to induce chemokines critical for monocyte recruitment. Mice lacking IL-33 have impaired recovery after CNS injury, which is associated with reduced myeloid cell infiltrates and decreased induction of M2 genes at the injury site. These results demonstrate a novel molecular mediator contributing to immune cell recruitment to the injured CNS and may lead to new therapeutic insights in CNS injury and neurodegenerative diseases.
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http://dx.doi.org/10.1016/j.neuron.2015.01.013DOI Listing
February 2015

Interactions of innate and adaptive immunity in brain development and function.

Brain Res 2015 Aug 7;1617:18-27. Epub 2014 Aug 7.

Center for Brain Immunology and Glia (BIG), Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA; Graduate Program in Neuroscience and Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, VA 22908, USA.

It has been known for decades that the immune system has a tremendous impact on behavior. Most work has described the negative role of immune cells on the central nervous system. However, we and others have demonstrated over the last decade that a well-regulated immune system is needed for proper brain function. Here we discuss several neuro-immune interactions, using examples from brain homeostasis and disease states. We will highlight our understanding of the consequences of malfunctioning immunity on neurodevelopment and will discuss the roles of the innate and adaptive immune system in neurodevelopment and how T cells maintain a proper innate immune balance in the brain surroundings and within its parenchyma. Also, we describe how immune imbalance impairs higher order brain functioning, possibly leading to behavioral and cognitive impairment. Lastly, we propose our hypothesis that some behavioral deficits in neurodevelopmental disorders, such as in autism spectrum disorder, are the consequence of malfunctioning immunity. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease.
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http://dx.doi.org/10.1016/j.brainres.2014.07.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320678PMC
August 2015

IL-4 in the brain: a cytokine to remember.

J Immunol 2012 Nov;189(9):4213-9

Department of Neuroscience and Graduate Program in Neuroscience, Center for Brain Immunology and Glia, University of Virginia, Charlottesville, VA 22908, USA.

IL-4 has been extensively studied in the context of its role in immunity. Accumulating evidence indicates, however, that it also plays a critical role in higher functions of the normal brain, such as memory and learning. In this review, we summarize current knowledge of the basic immunology of IL-4, describe how and where this cytokine appears to operate in normal brain function, and propose a hypothesis concerning its potential role in neurological pathologies.
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http://dx.doi.org/10.4049/jimmunol.1202246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481177PMC
November 2012