IL21 is a critical regulator of chronic/persistent but not acute/accelerated auto-immune and allo-immune responses
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1
University of Toledo, Medical Microbiology & Immunology, United States
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2
Baylor College of Medicine, United States
IL21 is critical for T1D development in NOD mice, but its role in sustaining T cell responses against islets during T1D progression remains unexplored. Our preliminary studies show that NOD mice produce high levels of serum IL21 during T1D onset. Thus, we hypothesize that IL21 produced by activated CD4 T cells in spontaneously diabetic NOD mice sustains T cell responses to islets. We show that IL21 is required for maintaining the function of auto-reactive immune cells during T1D progression as transient therapy with IL21 receptor fusion protein (IL21RFc) is effective in reversing T1D onset in NOD mice (n=11) and inducing long-term T1D remission for up to 30 weeks. Pancreatic infiltrates of IL21RFc-treated NOD mice contain mostly CD4 T cells, that have lost surface ICOS expression, and few CD8 T cells, suggesting that IL21RFc inhibits CD4 T cell help to CD8 T cells. In a parallel study, we also show that IL21 deficient mice are protected from chronic allograft vasculopathy in a MHC class-II mismatched cardiac allograft model. However, IL21 deficient mice acutely reject fully mismatched cardiac allografts, similar to wild type. Thus, we demonstrate a novel and critical role for IL21 signaling in driving chronic immune responses against auto and allo-antigens. Based on our findings, IL21 has the potential to act as a serum biomarker for early T1D detection and a therapeutic target to abrogate persistent T cell responses in T1D and chronic allograft rejection. We continue to investigate the molecular mechanisms governing IL21 mediated chronic immune responses.
Keywords:
T-cells,
type-1diabetes .,
Transplantation Immunology,
Immune Tolerance,
Cytokines
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Khattar
M,
Chen
W and
Stepkowski
S
(2013). IL21 is a critical regulator of chronic/persistent but not acute/accelerated auto-immune and allo-immune responses.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00097
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Received:
08 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Mithun Khattar, University of Toledo, Medical Microbiology & Immunology, Toledo, OH, 43614, United States, mithunkhattar@gmail.com
Prof. Stanislaw Stepkowski, University of Toledo, Medical Microbiology & Immunology, Toledo, OH, 43614, United States, stanislaw.Stepkowski@utoledo.edu