Rahul Sharma, PhD
Graduate School: University of Delhi, India
Primary Appointment: Associate Professor, Medicine, Nephrology
Research Interests: Regulatory T Cell deficiency; Sjogren's syndrome; Auto-immunity.
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Regulatory T cells (Treg) exert the major mechanism of peripheral tolerance. Treg deficiency causes early mortality in mice and humans due to multi-organ autoimmune syndrome. Most, if not all, autoimmune disorders are now being attributed to either numerical deficiency or functional inefficiency of the Tregs. We study the interplay of Treg and auto-reactive T cells, in terms of their homeostasis, effector function and migration/homing to the sites of inflammation. We have shown that IL-2 signaling plays an important role in all of these processes. For our studies, we use various mutant and knockout mice predisposed to autoimmune defects.
We have developed several rapid and efficient models of Treg deficiency based abnormalities that find applications in studies on autoimmune diseases such as allergic dermatitis, psoriasis, autoimmune pulmonary inflammation, Sjogren’s syndrome, type 1 diabetes and ulcerative colitis (inflammatory bowel disease). We demonstrated that Fas/FasL pathway is a major contributor to end–organ failure during autoimmunity and that IL-2 signaling acts as a modifier of the organ specificity of the autoimmune response. Blocking these pathways lead to prolongation of lifespan through diverse mechanisms. We study the mechanisms behind the IL-2 mediated regulation of these factors with a focus on trafficking of Tregs and auto-reactive T cells. The expression of Treg lineage transcription factor - Foxp3 is dependent on TCR signaling, IL-2 and Transforming Growth Factor-b1. Recently, we have found several novel pathways that can induce, restore or maintain Foxp3 expression independent of TCR, IL-2 and TGF-ß1. We study the molecular mechanisms behind these pathways with an aim to develop therapeutic approaches for inflammatory diseases.
Sharma R, Sung S-sJ, Fu SM and Ju ST. Regulation of multi-organ inflammation in the regulatory T cell-deficient scurfy mice. 2009 J. Biomed. Sci. 16: 20. PMC2653523.
Sharma R, Sung SS, Abaya CE, Ju AC, Fu SM, and Ju ST. 2009 IL-2 Regulates CD103 Expression on CD4+ T cells in Scurfy Mice That Display Both CD103-Dependent and Independent Inflammation. J Immunol. 2009 183:1065-73. PMC2734909.
Sharma R, Deshmukh US, Zheng L, Fu SM, and Ju ST. 2009 X-linked Foxp3 (Sf) Mutation Dominantly Inhibits Submandibular Gland Development and Inflammation Respectively through Adaptive and Innate Immune Mechanisms. J Immunol. 2009 183:3212-8. PMC2735024.
Kinsey GR, Sharma R, Huang L, Li L, Vergis A, Ye H, Ju ST and Okusa MD. Regulatory T cells suppress innate immunity in kidney ischemia reperfusion injury. J. Am Soc. Nephrol. 2009;20:1744-53. PMC2723989.
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