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<title lang=en>Ablation of interaction between IL-33 and ST2(+) regulatory T cells increases immune cell-mediated hepatitis and activated NK cell liver infiltration</title>
<creator>Noel, Gregory</creator>
<creator>Arshad, Muhammad Imran</creator>
<creator>Filliol, Aveline</creator>
<creator>Genet, Valentine</creator>
<creator>Rauch, Michel</creator>
<creator>Lucas-Clerc, Catherine</creator>
<creator>Lehuen, Agnes</creator>
<creator>Girard, Jean-Philippe</creator>
<creator>Piquet-Pellorce, Claire</creator>
<creator>Samson, Michel</creator>
<contributor>Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - 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 )</contributor>
<contributor>Laboratoire de biochimie générale ; Hôpital Pontchaillou - CHU Pontchaillou [Rennes]</contributor>
<contributor>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)</contributor>
<contributor>Institut de pharmacologie et de biologie structurale (IPBS) ; Université Paul Sabatier - Toulouse 3 (UPS) - Centre National de la Recherche Scientifique (CNRS)</contributor>
<contributor>INSERM</contributor>
<contributor> University of Rennes</contributor>
<contributor> Higher Education Commission (HEC) under NRPU scheme at University of Agriculture, Faisalabad, Pakistan [20-4613/NRPU/RD/HEC/14/45]</contributor>
<description>International audience</description>
<source>ISSN: 0193-1857</source>
<source>EISSN: 1522-1547</source>
<source>AJP - Gastrointestinal and Liver Physiology</source>
<publisher>American Physiological Society</publisher>
<identifier>hal-01366372</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01366372</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01366372/document</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01366372/file/Ablation%20of%20interaction%20between%20IL-33%20and%201%20ST2.pdf</identifier>
<source>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01366372</source>
<source>AJP - Gastrointestinal and Liver Physiology, American Physiological Society, 2016, 311 (2), pp.G313--G323. 〈10.1152/ajpgi.00097.2016〉</source>
<identifier>DOI : 10.1152/ajpgi.00097.2016</identifier>
<relation>info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpgi.00097.2016</relation>
<identifier>PUBMED : 27340126</identifier>
<relation>info:eu-repo/semantics/altIdentifier/pmid/27340126</relation>
<language>en</language>
<subject lang=en> hepatocytes</subject>
<subject lang=en> disease</subject>
<subject lang=en> signals</subject>
<subject lang=en> expression</subject>
<subject lang=en> alarmin</subject>
<subject lang=en>cytokine il-33</subject>
<subject lang=en> responses</subject>
<subject lang=en> tolerance</subject>
<subject lang=en> mice</subject>
<subject lang=en> accumulation</subject>
<subject>[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology</subject>
<subject>[SDV.IMM] Life Sciences [q-bio]/Immunology</subject>
<type>info:eu-repo/semantics/article</type>
<type>Journal articles</type>
<description lang=en>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-alpha and IL-1 beta 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.</description>
<date>2016</date>
</dc>
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