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Melissa A. Brown, PhDProfessor
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The tightly regulated expression of IL-4 by T cells and mast cells is a key factor for maintaining protective immunity. My research is focused in two areas: a) the study of mechanisms that control expression of Interleukin 4 (IL-4) in mast cells and T cells and b) determination of the role of mast cells in protective and pathological immune responses. The expression of IL-4 by mast cells is particularly interesting in view of recent studies demonstrating that mast cells play a critical role in gut and lung immunity. Mast cells present in these sites are potent producers of IL-4 and other cytokines and thus can influence many processes including the generation of T helper responses, B cell growth, differentiation and antibody production as well as the recruitment of inflammatory cells.
We are using a mast-cell deficient mouse model to examine the contribution of mast cells and mast cell cytokines to the pathology associated with several autoimmune diseases including diabetes and experimental allergic encephalomyelitis (EAE), the murine model of the human autoimmune disease, multiple sclerosis. The contributions of mast cells to the generation of protective immune responses to viral infections are also being explored using this model.
On IL-4 gene regulation...
Hural, J., M. Kwan, G. Henkel, M.B. Hock and M.A. Brown. An intron transcriptional enhancer regulates IL-4 gene locus accessibility in mast cells, J. Immunol. 165:3230-3249, 2000.
Weiss, D.L. and M.A. Brown. IL-4 gene regulation in mast cells: A paradigm of cell-type specific gene regulation. Immunol. Rev. 179:45-47, 2001.
Sherman, M.A., D. Powell and M.A. Brown. IL-4 induces the proteolytic processing mast cell STAT6. J. Immunol. 169:3811-3818, 2002.
Hock, M.B. and M.A. Brown. NFAT2 transactivation in mast cells: a novel isoform-specific domain confers unique FceRI responsiveness. J. Biol. Chem. 278:26695-26703, 2003.
Kwan, M., D. Powell, T.Y . Nachman and M.A. Brown. An intron GATA-binding site regulates chromatin accessibility and is essential for IL-4 gene expression in mast cells. Eur. J. Immunol.
35:1267-1274, 2005
Gregory, G.D., S.S. Raju, S. Winandy and M.A. Brown. Mast cell Il4 expression is regulated by Ikaros and influences encephalitogenic Th1 cell responses in EAE. J. Clin. Invest. 116:1327-1336, 2006.
On autoimmunity and mast cells...
Secor, V.H, W.E. Secor, C.A. Gutekunst and M.A. Brown. Mast cells contribute to the initiation and severity of disease in a murine model of multiple sclerosis. J.Exp. Med. 191:813-821, 2000.
Brown, M.A., M.Tanzola and M. Robbie. Mechanism underlying mast cell influence on EAE disease course. Mol. Immunol. 38:1373-1378, 2002.
Robbie-Ryan, M., M. Tanzola, V. Secor and M.A. Brown. Cutting Edge: Both activating and inhibitory Fc receptors on mast cells regulate disease severity, J. Immunol. 170:1630-1634, 2003.
Tanzola, M., M. Robbie-Ryan, C. Gutekunst and M.A. Brown. Mast cells exert effects outside the CNS to influence experimental allergic encephalomyelitis disease course, J. Immunol. 171:4385-4391, 2003.
Gregory, G.D., M. Robbie-Ryan, J. Sapbatino and M.A. Brown. Mast cells promote autoreactive T cell responses in a murine model f multiple sclerosis, Eur. J. Immunol. 35:348-3486, 2005.
Gregory, G.D., S.S. Raju, S. Winandy and M.A. Brown. Mast cell Il4 expression is regulated by Ikaros and influences encephalitogenic Th1 cell responses in EAE. J. Clin. Invest. 116:1327-1336, 2006.
Sayed, B.A. and M.A. Brown. Mast cells as modulators of T cell responses. Immunol. Rev. 217:53-64, 2007.
Christy, A.L. and M.A. Brown, The multitasking mast cell: positive and negative roles in the progression of autoimmunity. J. Immunol. 179:2673-2679, 2007.
Sayed, B.A., A.L. Christy, M.R. Quirion and M.A. Brown. Mast cells in Autoimmunity and Tolerance. Ann. Rev. Immunol. in press, 2008.
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View Publications by Melissa Brown listed in the National Library of Medicine (PubMed). |
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