Publications by authors named "Cedric Bosteels"

14 Publications

  • Page 1 of 1

CCR2- and Flt3-Dependent Inflammatory Conventional Type 2 Dendritic Cells Are Necessary for the Induction of Adaptive Immunity by the Human Vaccine Adjuvant System AS01.

Front Immunol 2020 14;11:606805. Epub 2021 Jan 14.

Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium.

The Adjuvant System AS01 contains monophosphoryl lipid A (MPL) and the saponin QS-21 in a liposomal formulation. AS01 is included in recently developed vaccines against malaria and varicella zoster virus. Like for many other adjuvants, induction of adaptive immunity by AS01 is highly dependent on the ability to recruit and activate dendritic cells (DCs) that migrate to the draining lymph node for T and B cell stimulation. The objective of this study was to more precisely address the contribution of the different conventional (cDC) and monocyte-derived DC (MC) subsets in the orchestration of the adaptive immune response after immunization with AS01 adjuvanted vaccine. The combination of MPL and QS-21 in AS01 induced strong recruitment of CD26XCR1 cDC1s, CD26CD172 cDC2s and a recently defined CCR2-dependent CD64-expressing inflammatory cDC2 (inf-cDC2) subset to the draining lymph node compared to antigen alone, while CD26CD64CD88 MCs were barely detectable. At 24 h post-vaccination, cDC2s and inf-cDC2s were superior amongst the different subsets in priming antigen-specific CD4 T cells, while simultaneously presenting antigen to CD8 T cells. Diphtheria toxin (DT) mediated depletion of all DCs prior to vaccination completely abolished adaptive immune responses, while depletion 24 h after vaccination mainly affected CD8 T cell responses. Vaccinated mice lacking Flt3 or the chemokine receptor CCR2 showed a marked deficit in inf-cDC2 recruitment and failed to raise proper antibody and T cell responses. Thus, the adjuvant activity of AS01 is associated with the potent activation of subsets of cDC2s, including the newly described inf-cDC2s.
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http://dx.doi.org/10.3389/fimmu.2020.606805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841299PMC
January 2021

Local immune response to food antigens drives meal-induced abdominal pain.

Nature 2021 Feb 13;590(7844):151-156. Epub 2021 Jan 13.

Laboratory for Intestinal Neuroimmune Interactions, Translational Research Center for Gastrointestinal Disorders, KU Leuven Department of Chronic Diseases, Metabolism and Ageing, Leuven, Belgium.

Up to 20% of people worldwide develop gastrointestinal symptoms following a meal, leading to decreased quality of life, substantial morbidity and high medical costs. Although the interest of both the scientific and lay communities in this issue has increased markedly in recent years, with the worldwide introduction of gluten-free and other diets, the underlying mechanisms of food-induced abdominal complaints remain largely unknown. Here we show that a bacterial infection and bacterial toxins can trigger an immune response that leads to the production of dietary-antigen-specific IgE antibodies in mice, which are limited to the intestine. Following subsequent oral ingestion of the respective dietary antigen, an IgE- and mast-cell-dependent mechanism induced increased visceral pain. This aberrant pain signalling resulted from histamine receptor H-mediated sensitization of visceral afferents. Moreover, injection of food antigens (gluten, wheat, soy and milk) into the rectosigmoid mucosa of patients with irritable bowel syndrome induced local oedema and mast cell activation. Our results identify and characterize a peripheral mechanism that underlies food-induced abdominal pain, thereby creating new possibilities for the treatment of irritable bowel syndrome and related abdominal pain disorders.
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http://dx.doi.org/10.1038/s41586-020-03118-2DOI Listing
February 2021

Case Report: Convalescent Plasma, a Targeted Therapy for Patients with CVID and Severe COVID-19.

Front Immunol 2020 20;11:596761. Epub 2020 Nov 20.

Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.

The disease course of COVID-19 in patients with immunodeficiencies is unclear, as well as the optimal therapeutic strategy. We report a case of a 37-year old male with common variable immunodeficiency disorder and a severe SARS-CoV-2 infection. After administration of convalescent plasma, the patient's condition improved rapidly. Despite clinical recovery, viral RNA remained detectable up to 60 days after onset of symptoms. We propose that convalescent plasma might be considered as a treatment option in patients with CVID and severe COVID-19. In addition, in patients with immunodeficiencies, a different clinical course is possible, with prolonged viral shedding.
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http://dx.doi.org/10.3389/fimmu.2020.596761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714937PMC
December 2020

Zilucoplan in patients with acute hypoxic respiratory failure due to COVID-19 (ZILU-COV): A structured summary of a study protocol for a randomised controlled trial.

Trials 2020 Nov 19;21(1):934. Epub 2020 Nov 19.

VIB Center for Inflammation Research, Ghent, Belgium and Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.

Objectives: Zilucoplan (complement C5 inhibitor) has profound effects on inhibiting acute lung injury post COVID-19, and can promote lung repair mechanisms that lead to improvement in lung oxygenation parameters. The purpose of this study is to investigate the efficacy and safety of Zilucoplan in improving oxygenation and short- and long-term outcome of COVID-19 patients with acute hypoxic respiratory failure.

Trial Design: This is a phase 2 academic, prospective, 2:1 randomized, open-label, multi-center interventional study.

Participants: Adult patients (≥18y old) will be recruited at specialized COVID-19 units and ICUs at 9 Belgian hospitals. The main eligibility criteria are as follows: 1) Inclusion criteria: a. Recent (≥6 days and ≤16 days) SARS-CoV-2 infection. b. Chest CT scan showing bilateral infiltrates within the last 2 days prior to randomisation. c. Acute hypoxia (defined as PaO/FiO below 350 mmHg or SpO2 below 93% on minimal 2 L/min supplemental oxygen). d. Signs of cytokine release syndrome characterized by either high serum ferritin, or high D-dimers, or high LDH or deep lymphopenia or a combination of those. 2) Exclusion criteria: e. Mechanical ventilation for more than 24 hours prior to randomisation. f. Active bacterial or fungal infection. g. History of meningococcal disease (due to the known high predisposition to invasive, often recurrent meningococcal infections of individuals deficient in components of the alternative and terminal complement pathways).

Intervention And Comparator: Patients in the experimental arm will receive daily 32,4 mg Zilucoplan subcutaneously and a daily IV infusion of 2g of the antibiotic ceftriaxone for 14 days (or until hospital discharge, whichever comes first) in addition to standard of care. These patients will receive additional prophylactic antibiotics until 14 days after the last Zilucoplan dose: hospitalized patients will receive a daily IV infusion of 2g of ceftriaxone, discharged patients will switch to daily 500 mg of oral ciprofloxacin. The control group will receive standard of care and a daily IV infusion of 2g of ceftriaxone for 1 week (or until hospital discharge, whichever comes first), to control for the effects of antibiotics on the clinical course of COVID-19.

Main Outcomes: The primary endpoint is the improvement of oxygenation as measured by mean and/or median change from pre-treatment (day 1) to post-treatment (day 6 and 15 or at discharge, whichever comes first) in PaO/FiO ratio, P(A-a)O gradient and a/A PO ratio. (PAO= Partial alveolar pressure of oxygen, PaO=partial arterial pressure of oxygen, FiO=Fraction of inspired oxygen).

Randomisation: Patients will be randomized in a 2:1 ratio (Zilucoplan: control). Randomization will be done using an Interactive Web Response System (REDCap).

Blinding (masking): In this open-label trial neither participants, caregivers, nor those assessing the outcomes will be blinded to group assignment.

Numbers To Be Randomised (sample Size): A total of 81 patients will be enrolled: 54 patients will be randomized to the experimental arm and 27 patients to the control arm.

Trial Status: ZILU-COV protocol Version 4.0 (June 10 2020). Participant recruitment started on June 23 2020 and is ongoing. Given the uncertainty of the pandemic, it is difficult to predict the anticipated end date.

Trial Registration: The trial was registered on Clinical Trials.gov on May 11, 2020 (ClinicalTrials.gov Identifier: NCT04382755 ) and on EudraCT (Identifier: 2020-002130-33 ).

Full Protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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http://dx.doi.org/10.1186/s13063-020-04884-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675383PMC
November 2020

Coronavirus disease 2019 in patients with inborn errors of immunity: An international study.

J Allergy Clin Immunol 2021 Feb 24;147(2):520-531. Epub 2020 Sep 24.

Garvan Institute of Medical Research, Darlinghurst, Australia; St Vincent's Clinical School, UNSW Sydney, Darlinghurst, Australia. Electronic address:

Background: There is uncertainty about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with rare inborn errors of immunity (IEI), a population at risk of developing severe coronavirus disease 2019. This is relevant not only for these patients but also for the general population, because studies of IEIs can unveil key requirements for host defense.

Objective: We sought to describe the presentation, manifestations, and outcome of SARS-CoV-2 infection in IEI to inform physicians and enhance understanding of host defense against SARS-CoV-2.

Methods: An invitation to participate in a retrospective study was distributed globally to scientific, medical, and patient societies involved in the care and advocacy for patients with IEI.

Results: We gathered information on 94 patients with IEI with SARS-CoV-2 infection. Their median age was 25 to 34 years. Fifty-three patients (56%) suffered from primary antibody deficiency, 9 (9.6%) had immune dysregulation syndrome, 6 (6.4%) a phagocyte defect, 7 (7.4%) an autoinflammatory disorder, 14 (15%) a combined immunodeficiency, 3 (3%) an innate immune defect, and 2 (2%) bone marrow failure. Ten were asymptomatic, 25 were treated as outpatients, 28 required admission without intensive care or ventilation, 13 required noninvasive ventilation or oxygen administration, 18 were admitted to intensive care units, 12 required invasive ventilation, and 3 required extracorporeal membrane oxygenation. Nine patients (7 adults and 2 children) died.

Conclusions: This study demonstrates that (1) more than 30% of patients with IEI had mild coronavirus disease 2019 (COVID-19) and (2) risk factors predisposing to severe disease/mortality in the general population also seemed to affect patients with IEI, including more younger patients. Further studies will identify pathways that are associated with increased risk of severe disease and are nonredundant or redundant for protection against SARS-CoV-2.
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http://dx.doi.org/10.1016/j.jaci.2020.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832563PMC
February 2021

Sargramostim to treat patients with acute hypoxic respiratory failure due to COVID-19 (SARPAC): A structured summary of a study protocol for a randomised controlled trial.

Trials 2020 Jun 5;21(1):491. Epub 2020 Jun 5.

VIB-UGent Inflammatie-researchcentrum, Oost-Vlaanderen, Ghent, Belgium.

Objectives: The hypothesis of the proposed intervention is that Granulocyte-macrophage colony-stimulating factor (GM-CSF) has profound effects on antiviral immunity, and can provide the stimulus to restore immune homeostasis in the lung with acute lung injury post COVID-19, and can promote lung repair mechanisms, that lead to a 25% improvement in lung oxygenation parameters. Sargramostim is a man-made form of the naturally-occurring protein GM-CSF.

Trial Design: A phase 4 academic, prospective, 2 arm (1:1 ratio), randomized, open-label, controlled trial.

Participants: Patients aged 18-80 years admitted to specialized COVID-19 wards in 5 Belgian hospitals with recent (< 2 weeks prior to randomization) confirmed COVID-19 infection and acute respiratory failure defined as a PaO2/FiO2 below 350 mmHg or SpO2 below 93% on minimal 2 L/min supplemental oxygen. Patients were excluded from the trial in case of (1) known serious allergic reactions to yeast-derived products, (2) lithium carbonate therapy, (3) mechanical ventilation prior to randomization, (4) peripheral white blood cell count above 25.000/μL and/or active myeloid malignancy, (5) high dose systemic steroid therapy (> 20 mg methylprednisolone or equivalent), (6) enrolment in another investigational study, (7) pregnant or breastfeeding or (8) ferritin levels > 2000 μg/mL.

Intervention And Comparator: Inhaled sargramostim 125 μg twice daily for 5 days in addition to standard care. Upon progression of disease requiring mechanical ventilation or to acute respiratory distress syndrome (ARDS) and initiation of mechanical ventilator support within the 5 day period, inhaled sargramostim will be replaced by intravenous sargramostim 125 μg/m body surface area once daily until the 5 day period is reached. From day 6 onwards, progressive patients in the active group will have the option to receive an additional 5 days of IV sargramostim, based on the treating physician's assessment. Intervention will be compared to standard of care. Subjects progressing to ARDS and requiring invasive mechanical ventilatory support, from day 6 onwards in the standard of care group will have the option (clinician's decision) to initiate IV sargramostim 125m μg/m body surface area once daily for 5 days.

Main Outcomes: The primary endpoint of this intervention is measuring oxygenation after 5 days of inhaled (and intravenous) treatment through assessment of a change in pretreatment and post-treatment ratio of PaO2/FiO2 and through measurement of the P(A-a)O2 gradient (PAO2= Partial alveolar pressure of oxygen, PaO2=Partial arterial pressure of oxygen; FiO2= Fraction of inspired oxygen).

Randomisation: Patients will be randomized in a 1:1 ratio. Randomization will be done using REDCap (electronic IWRS system).

Blinding (masking): In this open-label trial neither participants, caregivers, nor those assessing the outcomes will be blinded to group assignment.

Numbers To Be Randomised (sample Size): A total of 80 patients with confirmed COVID-19 and acute hypoxic respiratory failure will be enrolled, 40 in the active and 40 in the control group.

Trial Status: SARPAC protocol Version 2.0 (April 15 2020). Participant recruitment is ongoing in 5 Belgian Hospitals (i.e. University Hospital Ghent, AZ Sint-Jan Bruges, AZ Delta Roeselare, University Hospital Brussels and ZNA Middelheim Antwerp). Participant recruitment started on March 26 2020. Given the current decline of the COVID-19 pandemic in Belgium, it is difficult to anticipate the rate of participant recruitment.

Trial Registration: The trial was registered on Clinical Trials.gov on March 30, 2020 (ClinicalTrials.gov Identifier: NCT04326920) - retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT04326920?term=sarpac&recrs=ab&draw=2&rank=1 and on EudraCT on March 24th, 2020 (Identifier: 2020-001254-22).

Full Protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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http://dx.doi.org/10.1186/s13063-020-04451-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273817PMC
June 2020

Treatment of severely ill COVID-19 patients with anti-interleukin drugs (COV-AID): A structured summary of a study protocol for a randomised controlled trial.

Trials 2020 Jun 3;21(1):468. Epub 2020 Jun 3.

VIB-UGent Inflammatie-researchcentrum, Oost-Vlaanderen, Ghent, Belgium.

Objectives: The purpose of this study is to test the safety and effectiveness of individually or simultaneously blocking IL-6, IL-6 receptor and IL-1 versus standard of care on blood oxygenation and systemic cytokine release syndrome in patients with COVID-19 coronavirus infection and acute hypoxic respiratory failure and systemic cytokine release syndrome.

Trial Design: A phase 3 prospective, multi-center, interventional, open label, 6-arm 2x2 factorial design study.

Participants: Subjects will be recruited at the specialized COVID-19 wards and/or ICUs at 16 Belgian participating hospitals. Only adult (≥18y old) patients will be recruited with recent (≤16 days) COVID-19 infection and acute hypoxia (defined as PaO2/FiO2 below 350mmHg or PaO2/FiO2 below 280 on supplemental oxygen and immediately requiring high flow oxygen device or mechanical ventilation) and signs of systemic cytokine release syndrome characterized by high serum ferritin, or high D-dimers, or high LDH or deep lymphopenia or a combination of those, who have not been on mechanical ventilation for more than 24 hours before randomisation. Patients should have had a chest X-ray and/or CT scan showing bilateral infiltrates within the last 2 days before randomisation. Patients with active bacterial or fungal infection will be excluded.

Intervention And Comparator: Patients will be randomized to 1 of 5 experimental arms versus usual care. The experimental arms consist of Anakinra alone (anti-IL-1 binding the IL-1 receptor), Siltuximab alone (anti-IL-6 chimeric antibody), a combination of Siltuximab and Anakinra, Tocilizumab alone (humanised anti-IL-6 receptor antibody) or a combination of Anakinra with Tocilizumab in addition to standard care. Patients treated with Anakinra will receive a daily subcutaneous injection of 100mg for a maximum of 28 days or until hospital discharge, whichever comes first. Siltuximab (11mg/kg) or Tocilizumab (8mg/kg, with a maximum dose of 800mg) are administered as a single intravenous injection immediately after randomization.

Main Outcomes: The primary end point is the time to clinical improvement defined as the time from randomization to either an improvement of two points on a six-category ordinal scale measured daily till day 28 or discharge from the hospital or death. This ordinal scale is composed of (1) Death; (2) Hospitalized, on invasive mechanical ventilation or ECMO; (3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; (4) Hospitalized, requiring supplemental oxygen; (5) Hospitalized, not requiring supplemental oxygen; (6) Not hospitalized.

Randomisation: Patients will be randomized using an Interactive Web Response System (REDCap). A 2x2 factorial design was selected with a 2:1 randomization regarding the IL-1 blockade (Anakinra) and a 1:2 randomization regarding the IL-6 blockade (Siltuximab and Tocilizumab).

Blinding (masking): In this open-label trial neither participants, caregivers, nor those assessing the outcomes are blinded to group assignment.

Numbers To Be Randomised (sample Size): A total of 342 participants will be enrolled: 76 patients will receive usual care, 76 patients will receive Siltuximab alone, 76 patients will receive Tocilizumab alone, 38 will receive Anakinra alone, 38 patients will receive Anakinra and Siltuximab and 38 patients will receive Anakinra and Tocilizumab.

Trial Status: COV-AID protocol version 3.0 (15 Apr 2020). Participant recruitment is ongoing and started on April 4 2020. Given the current decline of the COVID-19 pandemic in Belgium, it is difficult to anticipate the rate of participant recruitment.

Trial Registration: The trial was registered on Clinical Trials.gov on April 1st, 2020 (ClinicalTrials.gov Identifier: NCT04330638) and on EudraCT on April 3rd 2020 (Identifier: 2020-001500-41).

Full Protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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http://dx.doi.org/10.1186/s13063-020-04453-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267751PMC
June 2020

Inflammatory Type 2 cDCs Acquire Features of cDC1s and Macrophages to Orchestrate Immunity to Respiratory Virus Infection.

Immunity 2020 06 8;52(6):1039-1056.e9. Epub 2020 May 8.

Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent 9052, Belgium; Department of Internal Medicine and Pediatrics, Ghent University, Ghent 9000, Belgium; Department of Pulmonary Medicine, Erasmus University Medical Center Rotterdam, Rotterdam 3015 GJ, the Netherlands. Electronic address:

The phenotypic and functional dichotomy between IRF8 type 1 and IRF4 type 2 conventional dendritic cells (cDC1s and cDC2s, respectively) is well accepted; it is unknown how robust this dichotomy is under inflammatory conditions, when additionally monocyte-derived cells (MCs) become competent antigen-presenting cells (APCs). Using single-cell technologies in models of respiratory viral infection, we found that lung cDC2s acquired expression of the Fc receptor CD64 shared with MCs and of IRF8 shared with cDC1s. These inflammatory cDC2s (inf-cDC2s) were superior in inducing CD4 T helper (Th) cell polarization while simultaneously presenting antigen to CD8 T cells. When carefully separated from inf-cDC2s, MCs lacked APC function. Inf-cDC2s matured in response to cell-intrinsic Toll-like receptor and type 1 interferon receptor signaling, upregulated an IRF8-dependent maturation module, and acquired antigens via convalescent serum and Fc receptors. Because hybrid inf-cDC2s are easily confused with monocyte-derived cells, their existence could explain why APC functions have been attributed to MCs.
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http://dx.doi.org/10.1016/j.immuni.2020.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7207120PMC
June 2020

Transcriptional regulation of DC fate specification.

Mol Immunol 2020 05 6;121:38-46. Epub 2020 Mar 6.

VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, Ghent, 9052, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. Electronic address:

Dendritic cells function in the immune system to instruct adaptive immune cells to respond accordingly to different threats. While conventional dendritic cells can be subdivided into two main subtypes, termed cDC1s and cDC2s, it is clear that further heterogeneity exists within these subtypes, particularly for cDC2s. Understanding the signals involved in specifying each of these lineages and subtypes thereof is crucial to (i) enable us to determine their specific functions and (ii) put us in a position to be able to target these cells to promote or prevent a specific function in any given disease setting. Although we still have much to learn regarding the specification of these cells, here we review the most recent advances in our understanding of this and highlight some of the next questions for the future.
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http://dx.doi.org/10.1016/j.molimm.2020.02.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187805PMC
May 2020

Twelve-year follow-up study after endoscopic sinus surgery in patients with chronic rhinosinusitis with nasal polyposis.

Clin Transl Allergy 2019 14;9:30. Epub 2019 Jun 14.

1Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a therapeutic challenge because of the high recurrence rate. Surgical intervention should be considered in patients who fail to improve after medical treatment. We monitored recurrence and revision surgery over 12 years after endoscopic sinus surgery in CRSwNP patients.

Methods: In this prospective cohort study, 47 patients with CRSwNP, who underwent primary or revision extended endoscopic sinus surgery, were followed. Clinical symptoms and total nasal endoscopic polyp score were evaluated before, 6 years and 12 years after surgery.

Results: Twelve years after surgery, 38 out of 47 patients (80.9%) were available for examination. There still was a significantly better symptom score and total nasal endoscopic polyp score compared to before surgery (P < 0.001). Within the 12-year follow-up period, 30 out of 38 patients developed recurrent nasal polyps, of which 14 patients underwent additional revision surgery. Comorbid allergic sensitization and tissue IL-5 levels were found to be significant predictors for the need of revision surgery.

Conclusions: This long-term cohort study, investigating the outcome after surgery in CRSwNP, showed that, despite the low number of patients, 78.9% of patients with CRSwNP were subject to recurrence of the disease and 36.8% to revision surgery over a 12-year period.
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http://dx.doi.org/10.1186/s13601-019-0269-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6570859PMC
June 2019

Isolation of Conventional Murine Lung Dendritic Cell Subsets.

Curr Protoc Immunol 2018 02 21;120:3.7B.1-3.7B.16. Epub 2018 Feb 21.

Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium.

The lungs are continuously exposed to environmental threats, requiring an adequate and stringent immune response of a heterogeneous set of effector cells. Dendritic cells (DCs) form a dense network in the respiratory mucosa and act as the central regulators of the different components of this response, both sensing the nature of the threats and precisely coordinating the effector mechanisms best suited for overcoming it. The DCs are classically subdivided in two main groups, plasmacytoid DCs (pDCs) and conventional DCs (cDCs), the latter being further subdivided into cDC1s and cDC2s based on ontogeny and their distinct non-redundant functions. This protocol provides different enrichment methods and represents an up-to-date, universal framework that uses a minimal set of highly specific lineage markers to discriminate and sort pure cDC subsets from the murine lung but also across tissues and species which is an added value in intra- and interspecies comparative research. © 2018 by John Wiley & Sons, Inc.
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http://dx.doi.org/10.1002/cpim.39DOI Listing
February 2018

Epitope mapping and kinetics of CD4 T cell immunity to pneumonia virus of mice in the C57BL/6 strain.

Sci Rep 2017 06 14;7(1):3472. Epub 2017 Jun 14.

Laboratory of Immunoregulation and Mucosal Immunology, VIB Center for Inflammation Research, Ghent, Belgium.

Pneumonia virus of mice (PVM) infection has been widely used as a rodent model to study the closely related human respiratory syncytial virus (hRSV). While T cells are indispensable for viral clearance, they also contribute to immunopathology. To gain more insight into mechanistic details, novel tools are needed that allow to study virus-specific T cells in C57BL/6 mice as the majority of transgenic mice are only available on this background. While PVM-specific CD8 T cell epitopes were recently described, so far no PVM-specific CD4 T cell epitopes have been identified within the C57BL/6 strain. Therefore, we set out to map H2-IA-restricted epitopes along the PVM proteome. By means of in silico prediction and subsequent functional validation, we were able to identify a MHCII-restricted CD4 T cell epitope, corresponding to amino acids 37-47 in the PVM matrix protein (M). Using this newly identified MHCII-restricted M epitope and a previously described MHCI-restricted N epitope, we generated peptide-loaded MHCII and MHCI tetramers and characterized the dynamics of virus-specific CD4 and CD8 T cell responses in vivo. The findings of this study can provide a basis for detailed investigation of T cell-mediated immune responses to PVM in a variety of genetically modified C57BL/6 mice.
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http://dx.doi.org/10.1038/s41598-017-03042-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471230PMC
June 2017