My research interests are focused on two areas:
- the induction and regulation of autoimmunity and
- antigen processing and presentation.
These studies are based on the rat adjuvant arthritis (AA) model of human rheumatoid arthritis (RA). The 65-kD heat-shock protein (hsp65) has been implicated in the pathogenesis of AA as well as RA. Lewis rats (RT.1l) are highly susceptible to AA, whereas Wistar Kyoto rats of the same major histocompatibility complex (MHC) haplotype are resistant. The focus of my current research in AA is on:
- the mechanism of diversification of response to hsp65 and its involvement in natural remission from acute arthritis;
- the immunological basis of susceptibility/resistance to arthritis of defined inbred rat strains;
- the dynamics of cytokine responses during the course of arthritis and the novel aspects of cytokine crossregulation in vivo;
- the factors influencing the target organ susceptibility in autoimmune arthritis;
- the role of T helper 17 (Th17) and CD4+CD25+Foxp3+regulatory T cells in the pathogenesis of arthritis; and
- the development of novel immunomodulatory and therapeutic approaches for arthritis, including the use of natural products belonging to the traditional systems of medicine.
In parallel, studies are underway to define the T cell as well as the B cell epitopes within hsp65 that are of relevance in the initiation, progression and regression of arthritis. I believe that the results of these studies would contribute significantly to advancing our understanding of the pathogenesis of autoimmune diseases, and to devising novel therapeutic strategies for these debilitating disorders.
Selected Recent Publications
Yu H, Lu C, Tan MT, Moudgil KD. Comparative antigen-induced gene expression profiles unveil novel aspects of susceptibility/resistance to adjuvant arthritis in rats. Mol Immunol. 2013, 56(4):531-539.
Nanjundaiah SM, Venkatesha SH, Yu H, Tong L, Stains JP, Moudgil KD. Celastrus and its bioactive Celastrol protect against bone damage in autoimmune arthritis by modulating the osteo-immune crosstalk. J Biol Chem. 2012, 287: 22216.
Yang Y-H, Rajaiah R, Ruoslahti E, and Moudgil, KD. Peptides targeting inflamed synovial vasculature attenuate autoimmune arthritis. Proc. Natl. Acad. Sci. USA 2011, 108: 12857.
Rajaiah R, Puttabyatappa M, Polumuri SK, Moudgil KD. Interleukin-27 and interferon-gamma are involved in regulation of autoimmune arthritis. J Biol Chem. 2011;286(4):2817.
Venkatesha SH, Yu H, Rajaiah R, Tong L, Moudgil KD. Celastrus-derived celastrol suppresses autoimmune arthritis by modulating antigen-induced cellular and humoral effector responses. J Biol Chem. 2011;286(17):15138.
Yu H, Yang YH, Rajaiah R, Moudgil KD. Nicotine-induced differential modulation of autoimmune arthritis in the Lewis rat involves changes in interleukin-17 and anti-cyclic citrullinated peptide antibodies. Arthritis Rheum. 2011 Apr;63(4):981. doi: 10.1002/art.30219.
Huang M.N., H. Yu and K.D. Moudgil. The involvement of heat-shock proteins in the pathogenesis of autoimmune arthritis: a critical appraisal. Semin. Arthritis Rheum. 2010:40: 164.
Rajaiah R. and K.D. Moudgil. Heat-shock protein can promote as well as regulate autoimmunity. Autoimmun. Rev. 2009, 8: 388.
Satpute S.R., R. Rajaiah, S.K. Polumuri and K.D. Moudgil. Tolerization with Hsp65 induces protection against adjuvant-induced arthritis by modulating the antigen-directed interferon-gamma, interleukin-17 and antibody responses. Arthritis Rheum. 2009, 60: 103.
Kim E.K. and K.D. Moudgil. The determinants of susceptibility/resistance to adjuvant arthritis in rats. Arthritis Res. Therapy 2009, 11(4): 239.
Durai M., M.N. Huang, and K.D. Moudgil. Self heat-shock protein 65-mediated regulation of autoimmune arthritis. J. Autoimmun. 2009 Oct 1. [Epub ahead of print].
Rajaiah R., D.Y. Lee, Z. Ma, A.Y. Fan, L. Lao, H.H. Fong, B.M. Berman, and K.D. Moudgil. Huo-Luo-Xiao-Ling Dan modulates antigen-directed immune response in adjuvant-induced inflammation. J. Ethnopharmacol. 2009, 123(1): 40.
Rajaiah, R., Y. Yang, S.R. Satpute, M. Durai, and K.D. Moudgil. Immunopathogenesis and Treatment of Autoimmune Arthritis in Animal Models, In: Recent Research Developments on Rheumatic Diseases (edited by Antonio La Cava, MD, PhD, UCLA, Los Angeles, CA, USA), Research Signpost Publishers, 2009, Ch. 1.
Moudgil, K.D. and M. Durai. Regulation of autoimmune arthritis by self heat-shock proteins. Trends. Immunol. 2008, 29: 412.
Mia M.Y., E.Y. Kim, S.R. Satpute, and K.D. Moudgil. The Dynamics of Articular Leukocyte Trafficking and the Immune Response to Self Heat-Shock Protein 65 Influence Arthritis Susceptibility. J. Clin. Immunol. 2008, 28: 420.
Kim E.Y., H.H. Chi, R. Rajaiah, and K.D. Moudgil. Exogenous tumor necrosis factor-alpha induces suppression of autoimmune arthritis. Arthritis Res. Ther. 2008, 10: R38.
Kim, E.Y., H.H. Chi, M. Bouziane, A. Gaur, and K.D. Moudgil. Regulation of autoimmune arthritis by the pro-inflammatory cytokine interferon-gamma. Clin. Immunol. 2008, 127: 98-106.
Kim E. and K. D. Moudgil. Regulation of autoimmune inflammation by pro-inflammatory cytokines. Immunol. Lett. 2008, 120: 1.
Satpute, S.R., M. Durai, K.D. Moudgil. Antigen-Specific Tolerogenic and Immunomodulatory Strategies for the treatment of Autoimmune Arthritis. Semin Arthritis Rheum 2008, 38(3):195.
Kim H. R., R. Rajaiah, Q-L Wu, S. R. Satpute, M. T. Tan, J. E. Simon, B. M. Berman, and K. D. Moudgil. Green tea affords protection against autoimmune arthritis in rats by modulating the disease-related immune events. J. Nutrition 2008, 138: 2111.
Coelho, V., F. Broere, R. J. Binder, Y. Shoenfeld, and K.D. Moudgil. Heat-shock proteins: pro-inflammatory versus regulatory attributes. Cell Stress Chaperones 2008, 13: 119.
Rajaiah R. and K.D. Moudgil. Animal Models, In: Rheumatoid Arthritis (eds. M.C. Hochberg, A.J. Silman, J.S. Smolen, M.H. Weisman, and M.E. Weinblatt), Mosby, Inc., an affiliate of Elsevier, Inc., 2008, Ch. 8N.
Satpute, S., N. Soukhareva, D.W. Scott, and K.D. Moudgil. Mycobacterial hsp65-IgG-expressing tolerogenic B cells induce protection against adjuvant arthritis in the Lewis rat. Arthritis and Rheumatism 2007, 56: 1490.
Durai, M., H.R. Kim, K. Bala, and K.D. Moudgil. T Cells Against the Pathogenic and Protective Epitopes of Heat-shock Protein 65 Are Crossreactive and Display Functional Similarity: Novel Aspect of Regulation of Autoimmune Arthritis. J. Rheumatol 2007, 34: 2134.
Tong, L. and K.D. Moudgil. Celastrus aculeatus Merr. suppresses the induction and progression of autoimmune arthritis by modulating immune response to heat-shock protein 65. Arthritis Res. Therapy 2007, 9: R70.
Sinha, P., J.A. Snyder, E. Y. Kim, and K. D. Moudgil. The Major Histocompatibility Complex Haplotypes Dictate and the Background Genes Fine-tune the Dominant versus the Cryptic Response Profile of a T-cell Determinant within a Native Antigen: Relevance to Disease Susceptibility and Vaccination. Scand. J. Immunol. 2007, 65: 158.
Kim, H. R., E. Y. Kim, J. Cerny, and K. D. Moudgil. Antibody responses to mycobacterial and self heat-shock protein 65 in autoimmune arthritis: epitope specificity and implication in pathogenesis. J. Immunol. 2006, 177: 6634.
Jiang, X. and K. D. Moudgil. The unveiling of hidden T cell determinants of a native antigen by defined mediators of inflammation: implications for the pathogenesis of autoimmunity. Scand. J. Immunol. 2006, 63: 338.
Bala K. K. and K. D. Moudgil. Induction and maintenance of self tolerance: the role of CD4+CD25+ regulatory T cells. Arch. Immunol. Ther. Exp. 2006, 54: 307.
Zhu, H., K. Liu, J. Cerny, T. Imoto, and K. D. Moudgil. Insertion of the dibasic motif in the flanking region of a cryptic self-determinant leads to activation of the epitope-specific T cells. J. Immunol 2005, 175: 2252.
Mia, M. Y., M. Durai, H. R. Kim, and K. D. Moudgil. Heat shock protein 65-reactive T cells are involved in the pathogenesis of non-antigenic dimethyl dioctadecyl ammonium bromide-induced arthritis. J Immunol 2005, 175: 219.
Moudgil, K. D., and E. E. Sercarz. Understanding crypticity is the key to revealing the pathogenesis of autoimmunity. Trends Immunol 2005, 26:355.
Durai, M., H.R. Kim, and K.D. Moudgil. The regulatory C-terminal determinants within mycobacterial heat shock protein 65 are cryptic and cross-reactive with the dominant self homologs: implications for the pathogenesis of autoimmune arthritis. J. Immunol. 2004, 173: 181.
Sinha, P., H.H. Chi, H.R. Kim, B.E. Clausen, B. Pederson, E.E. Sercarz, I. Forster and K.D. Moudgil. Mouse lysozyme-M knockout mice reveal how the self determinant hierarchy shapes the T cell repertoire against this circulating self antigen in wild type mice. J. Immunol. 2004, 173: 1763.
Durai, M., R.S. Gupta, and K.D. Moudgil. The T cells specific for the carboxyl-terminal determinants of self(rat) heat-shock protein 65 escape tolerance induction and are involved in regulation of autoimmune arthritis. J. Immunol. 2004, 172: 2795
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