Faculty, Graduate Program
Adjunct Professor, UCSD Department of Medicine
Regulation Of Immune Responses At Epithelial Interfaces
We have a long-term interest in interactions between intraepithelial γδ T cells and their neighboring epithelial cells. Epithelial tissues including the skin, intestine and lungs are the first point of contact between the immune system and the outside world. The intraepithelial γδ T cells provide a first line of defense in these tissues. Our results have defined unique properties of these cells and support a specialized role for epithelial γδ T cells in immune surveillance, wound repair, inflammation, and protection from malignancy. We have identified cell surface molecules and growth factors that regulate epithelial T cell functional responses that have increased our understanding of the role that these cells play in epithelial and mucosal diseases such as inflammatory bowel disease, asthma, malignancies and wound healing. Chronic wounds are a debilitating problem and new information gained from these studies will be utilized to modulate γδ T cell responses and develop new strategies to accelerate healing.
Ph.D., Immunology, The University of Chicago, 1986
B.S., Zoology, Duke University, 1977
Lucille P. Markey Scholar in Biomedical Science, 1989-1996
Leukemia Society of America Scholar, 1996-2001
Stohlman Scholar Award, Leukemia and Lymphoma Society, 2001
Honorary Doctoral Degree, University of Copenhagen, 2010
Jameson, J., Ugarte, K., Chen, N., Yachi, P., Fuchs, E., Boismenu, R., Havran, W.L. A role for skin γδ T cells in wound healing. Science 296:747-749, 2002.
Chen, Y., Chou, K., Fuchs, E., Havran, W.L., Boismenu, R. Protection of the intestinal mucosa by intraepithelial γδ T cells. Proc. Nat. Acad. Sci. USA, 99:14338-14343, 2002.
Jameson, J., Cauvi, G., Witherden, D., and Havran, W.L. A keratinocyte-responsive γδ TCR is necessary for dendritic epidermal T cell activation by damaged keratinocytes and maintenance in the epidermis. J. Immunol., 172:3573-3579, 2004.
Sharp, L.*, Jameson, J.*, Cauvi, G., and Havran, W.L. Dendritic epidermal T cells regulate skin homeostasis through local production of Insulin Like Growth Factor-1. Nature Immunol. 6:73-79, 2004.
Jameson, J., Cauvi, G., Sharp, L., Witherden, D., and Havran, W.L. γδ T cell-induced hyaluronan production by epithelial cells regulates inflammation. J. Exp. Med. 201:1269-1279, 2005.
Kim, C-H., Witherden, D.A., and Havran, W.L. Characterization and TCR variable region gene use of mouse resident nasal γδ T lymphocytes. J Leukocyte Biol, 84:1259-1263, 2008.
Toulon, A., Breton, L., Taylor, K.R., Tenenhaus, M., Bhavsar, D., Lanigan, C., Rudolph, R., Jameson, J., and Havran, W.L. A role for human skin resident T cells in wound healing. J.Exp.Med. 206:743-50, 2009.
Witherden, D.A., Verdino, P., Rieder, S.E., Garijo, O., Mills, R.E., Teyton, L., Fischer, W.H., Wilson, I.A., and Havran, W.L. The adhesion molecule JAML is a costimulatory receptor for epithelial γδ T cell activation. Science, 329:1205-1210, 2010.
Verdino, P., Witherden, D.A., Havran, W.L. and Wilson, I.A. The molecular interaction of CAR and JAML recruits the central cell signal transducer PI3K. Science, 329:1210-1214, 2010.
Verdino, P., Witherden, D.A., Ferguson, M.S., Corper, A.L., Schiefner, A., Havran, W.L., and Wilson, I.A. Molecular insights into γδ T-cell costimulation by an anti-JAML antibody. Structure 19:80-89, 2011.
Verdino, P., Witherden, D.A., Podshivalova, K., Rieder, S.E., Havran, W.L., and Wilson, I.A. cDNA sequence and Fab crystal structure of HL4E10, a hamster IgG lambda light chain antibody stimulatory for γδ T cells. PLOS One 6:e19828:1-10, 2011.
Komori, H.K., Witherden, D.A., Kelly, R., Sendaydiego, K., Jameson, J.M., Teyton, L., and Havran, W.L. Dendritic epidermal γδ T cell ligands are rapidly and locally expressed by keratinocytes following cutaneous wounding. J Immunol. Cutting Edge 188: 2972-2976, 2012.
Witherden, D.A., Watanabe, M., Garijo, O., Rieder, S.E., Sarkisyan, G., Cronin, S.J.F., Verdino, P., Wilson, I.A., Kumanogoh, A., Kikutani, H., Teyton, L., Fischer, W.H. and Havran, W.L. The CD100 receptor interacts with its Plexin B2 ligand to regulate epidermal γδ T cell function. Immunity 37:314-325, 2012.
MacLeod, A.S., Hemmers, S., Garijo, O, Chabod, M., Mowen, K., Witherden, D.A., and Havran, W.L. Dendritic epidermal T cells regulate skin antimicrobial barrier function. J. Clinical Investigation 123: 4364-4374, 2013.
Meehan, T.F., Witherden, D.A., Kim, C.H., Komori, H.K., Kumanogoh, A., Kikutani, H., Eckmann, L., and Havran, W.L. Protection against colitis by CD100-dependent modulation of intraepithelial γδ T lymphocyte function. Mucosal Immunology 7:134-142, 2014.