My project focuses on the contribution of the cell-surface receptor Tim-1 to helper CD4+ T cell function. Tim-1 is expressed by activated CD4+ T cells, dendritic cells, and B cells. Tim-1 polymorphisms in mice and humans have been implicated in allergic immune responses. Blocking antibodies to Tim-1 have been shown in mice to decrease airway hyperreactivity in a model of Th2 T cell-driven airway hyperreactivity. However, the role of Tim-1 as a general costimulatory molecule has also been postulated, and antibodies to Tim-1 have been shown to decrease disease in a mouse model of multiple sclerosis, a Th1/Th17-driven disease. Several groups have also demonstrated that Tim-1 may bind phosphatidylserine, a membrane lipid exposed on apoptotic cells. Impaired clearance of apoptotic cells is implicated in the development of autoimmune disease, further expanding the possible role that Tim-1 may play in immune system activation and regulation. Our goal is to characterize the role of Tim-1 in immune responses.

Curtiss ML, Gorman JV, Businga TR, Traver G, Singh M, Meyerholz DK, Kline JN, Murphy AJ, Valenzuela DM, Colgan JD, Rothman PB, Cassel SL. Tim-1 regulates Th2 responses in an airway hypersensitivity model. Eur J Immunol. 2012 Mar;42(3):651-61. doi: 10.1002/eji.201141581. PubMed PMID: 22144095.

Curtiss ML, Hostager BS, Stepniak E, Singh M, Manhica N, Knisz J, Traver G, Rennert PD, Colgan JD, Rothman PB. Fyn binds to and phosphorylates T cell immunoglobulin and mucin domain-1 (Tim-1). Mol Immunol. 2011 Jul;48(12-13):1424-31. Epub 2011 Apr 21. PubMed PMID: 21513984; PubMed Central PMCID: PMC3109159.

Collins M, Tremblay M, Chapman N, Curtiss M, Rothman PB, Houtman JC. The T cell receptor-mediated phosphorylation of Pyk2 tyrosines 402 and 580 occurs via a distinct mechanism than other receptor systems. J Leukoc Biol. 2010 Apr;87(4):691-701. Epub 2009 Dec 22. PubMed PMID: 20028775.

Curtiss M, Colgan J. The role of the T-cell costimulatory molecule Tim-1 in the immune response. Immunol Res. 2007;39(1-3):52-61. Review. PubMed PMID:17917055.