Ablation of interaction between IL-33 and ST2(+) regulatory T cells increases immune cell-mediated hepatitis and activated NK cell liver infiltration

Autor: Catherine Lucas-Clerc, Agnès Lehuen, Muhammad Imran Arshad, Michel Samson, Valentine Genet, Gregory Noel, Claire Piquet-Pellorce, Michel Rauch, Aveline Filliol, Jean-Philippe Girard
Přispěvatelé: Institut de recherche, santé, environnement et travail ( Irset ), Université d'Angers ( UA ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -École des Hautes Études en Santé Publique [EHESP] ( EHESP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Université des Antilles ( UA ), Laboratoire de biochimie générale, Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de pharmacologie et de biologie structurale ( IPBS ), Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, INSERM, University of Rennes, Higher Education Commission (HEC) under NRPU scheme at University of Agriculture, Faisalabad, Pakistan [20-4613/NRPU/RD/HEC/14/45], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Chard-Hutchinson, Xavier, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3)
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Physiology
medicine.medical_treatment
CXCR3
Lymphocyte Activation
T-Lymphocytes
Regulatory
Hepatitis
Interleukin 21
0302 clinical medicine
Concanavalin A
[ SDV.IMM ] Life Sciences [q-bio]/Immunology
IL-2 receptor
Cells
Cultured
Liver injury
Mice
Knockout
tolerance
Gastroenterology
signals
alarmin
3. Good health
Killer Cells
Natural
Chemotaxis
Leukocyte
Cytokine
Phenotype
Liver
Cytokines
[SDV.IMM]Life Sciences [q-bio]/Immunology
hepatocytes
[ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Chemical and Drug Induced Liver Injury
Inflammation Mediators
Signal Transduction
medicine.medical_specialty
mice
[SDV.IMM] Life Sciences [q-bio]/Immunology
Biology
03 medical and health sciences
Immune system
Physiology (medical)
Internal medicine
expression
medicine
Animals
Genetic Predisposition to Disease
disease
Hepatology
cytokine il-33
[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
medicine.disease
Interleukin-33
Interleukin-1 Receptor-Like 1 Protein
[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Interleukin 33
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
Endocrinology
responses
accumulation
CD8
030215 immunology
Zdroj: AJP-Gastrointestinal and Liver Physiology
AJP-Gastrointestinal and Liver Physiology, American Physiological Society, 2016, 311 (2), pp.G313--G323. 〈10.1152/ajpgi.00097.2016〉
AJP-Gastrointestinal and Liver Physiology, 2016, 311 (2), pp.G313--G323. ⟨10.1152/ajpgi.00097.2016⟩
AJP-Gastrointestinal and Liver Physiology, American Physiological Society, 2016, 311 (2), pp.G313--G323. ⟨10.1152/ajpgi.00097.2016⟩
ISSN: 0193-1857
1522-1547
DOI: 10.1152/ajpgi.00097.2016〉
Popis: The IL-33/ST2 axis plays a protective role in T-cell-mediated hepatitis, but little is known about the functional impact of endogenous IL-33 on liver immunopathology. We used IL-33-deficient mice to investigate the functional effect of endogenous IL-33 in concanavalin A (Con A)-hepatitis. IL-33−/− mice displayed more severe Con A liver injury than wild-type (WT) mice, consistent with a hepatoprotective effect of IL-33. The more severe hepatic injury in IL-33−/− mice was associated with significantly higher levels of TNF-α and IL-1β and a larger number of NK cells infiltrating the liver. The expression of Th2 cytokines (IL-4, IL-10) and IL-17 was not significantly varied between WT and IL-33−/− mice following Con A-hepatitis. The percentage of CD25+ NK cells was significantly higher in the livers of IL-33−/− mice than in WT mice in association with upregulated expression of CXCR3 in the liver. Regulatory T cells (Treg cells) strongly infiltrated the liver in both WT and IL-33−/− mice, but Con A treatment increased their membrane expression of ST2 and CD25 only in WT mice. In vitro, IL-33 had a significant survival effect, increasing the total number of splenocytes, including B cells, CD4+ and CD8+ T cells, and the frequency of ST2+ Treg cells. In conclusion, IL-33 acts as a potent immune modulator protecting the liver through activation of ST2+ Treg cells and control of NK cells.
Databáze: OpenAIRE
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