| A non-redundant role for OX40 in the competitive fitness of Treg in response to IL-2. | |
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MedLine Citation:
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PMID: 20806292 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OX40 stimulation is known to enhance activation of effector T cells and to inhibit induction and suppressive function of Treg. Here we uncovered a novel role of OX40 in sustaining Treg competitive fitness in vivo, during repopulation of lymphopenic hosts and reconstitution of BM chimeras. Defective expansion of OX40-null Treg diminished their ability to suppress inflammation in a model of lymphopenia-driven colitis. OX40-mediated promotion of Treg fitness spanned beyond lymphopenic environments, as endogenous Treg in OX40-null mice showed decreased accumulation during thymic development, enhanced susceptibility to antibody-mediated depletion and defective turnover following thymectomy. In vitro, OX40-deficient Treg were found to be intrinsically hyporesponsive to IL-2, in terms of Stat5 phosphorylation and proliferation, according to elevated SOCS1 content and reduced miR155 expression. Therefore, OX40 is a key factor in shaping Treg sensitivity to IL-2 and promoting their proliferation and survival, toward accurate immune regulation. |
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Authors:
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Silvia Piconese; Paola Pittoni; Alessia Burocchi; Andrea Gorzanelli; Alessandra Carè; Claudio Tripodo; Mario P Colombo |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of immunology Volume: 40 ISSN: 1521-4141 ISO Abbreviation: Eur. J. Immunol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-11-01 Completed Date: 2010-12-16 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1273201 Medline TA: Eur J Immunol Country: Germany |
Other Details:
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Languages: eng Pagination: 2902-13 Citation Subset: IM |
Affiliation:
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Molecular Immunology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Cell Proliferation Colitis / immunology* Flow Cytometry Interleukin-2 / immunology* Lymphopenia / immunology* Male Mice Mice, Inbred C57BL Mice, Knockout Phosphorylation / immunology Radiation Chimera Receptors, OX40 / immunology* STAT5 Transcription Factor / immunology Specific Pathogen-Free Organisms Suppressor of Cytokine Signaling Proteins / immunology T-Lymphocytes, Regulatory / immunology* |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-2; 0/Receptors, OX40; 0/STAT5 Transcription Factor; 0/Socs1 protein, mouse; 0/Suppressor of Cytokine Signaling Proteins; 0/Tnfrsf4 protein, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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