Professor of Physiology
Dr. Wira received his B.S. in 1962 in Animal Husbandry from Delaware Valley College, Doylestown, PA and his M.S. in Physiology from Michigan State University in 1966. Dr. Wira came to Dartmouth in 1966 where he received his Ph.D. in 1970. From 1970 to 1972 he did his post- doctoral training at the University of Paris, France, studying molecular mechanism of estrogen action in the uterus. He then returned to Dartmouth as an Assistant Professor in the Department of Physiology until 1978 when he was promoted to Associate Professor. In 1985 he was promoted to Professor.
Since 1975, Dr. Wira has studied how female sex hormones influence mucosal immunity in the female reproductive tract. Research that Dr. Wira and associates carried out in the late 1970s and early 1980s showed that levels of IgA and IgG, antibodies which respond to antigens as part of the mucosal immune system in the female genital tract, are regulated by sex hormones, and that the levels vary depending on the stage of the reproductive cycle. This research demonstrated that the receptor for IgA, called secretory component, is also regulated by sex hormones.
In other studies, Dr. Wira has found that IgA and IgG antibodies in uterine and cervico-vaginal secretions are in part, derived from the gastrointestinal tract. He also found that intrauterine immunization can result in a pronounced antibody immune response within the uterine tract. Research efforts are presently focused on looking specifically IgA transport through epithelial cells, the role of cytokines (interferon-gamma, TNF-alpha and the interleukins) in regulating immune responses and the expression of cytokine message and protein in the female reproductive tract. Recent studies indicate that the female genital tract is an inductive site for immune responses and that estradiol and progesterone regulate antigen presentation by epithelial and stromal cells in the uterus and vagina. These studies have important implications in both the protection against and the control of infections by virus and bacteria.
Dr Wira has recently been awarded a Program Project grant by the National Institute of Allergy and Infectious Disease, NIH, that is designed to increase the presently limited knowledge of immune protection of the human female reproductive tract. This project represents a major collaborative effort between the Immunology and Endocrinology Programs at Dartmouth Hitchcock Medical Center to characterize immune functions in the Fallopian tube, uterus, cervix and vagina and to define the roles of steroid hormones and cytokines in mucosal immune regulation. The foundations for this Program Project were laid by Dr. Wira's earlier research on the secretory immune system in the female reproductive tract of the rat. These studies will increase the presently limited knowledge of immune protection of the human female reproductive tract and should provide basic information essential for prevention of local infection in the genital mucosa, for management of sexually transmitted diseases, and for understanding the heterosexual transmission of HIV-1.
Wira, C.R., Kaushic, C. and Richardson, J.M. Role of sex hormones and cytokines in regulating the mucosal immune system in the female reproductive tract. In: Handbook of Mucosal Diseases. (Ogra, P.L., Mestecky, J., Lamm, M.E., Strober, W., McGhee, J.R. and Bienenstock, J. eds.) Academic Press, NY. Chapter 92, pp. 1449-1461, 1999.
Kaushic, C., Zhou, F., Murdin, A.D. and Wira, C.R. Effects of estradiol and progesterone on susceptibility and early immune responses to Chlamydia trachomatis infection in the female reproductive tract. Infect. Immun. 68:4207-4216, 2000.
Kaushic, C., Grant, K., Crane, M. and Wira, C.R. Infection of polarized primary epithelial cells from rat uterus with Chlamydia trachomatis: Cell-cell interaction and cytokine secretion. Am. J. Reprod. Immunol. 44:73-79, 2000.
Wira, C.R., Rossoll R.M. and Kaushic, C. Antigen presenting cells in the female reproductive tract: Influence of estradiol on antigen presentation by vaginal cells. Endocrinol. 141(8):2877-2885, 2000.
Wallace, P.K., Yeaman, G.R., Kristy Johnson, K., Collins, J.E., Guyre, P.M. and Wira, C.R. MHC Class II Expression and Antigen Presentation by Endometrium Cells. J.Steroid Biochem. Mol. Biol. 76(1-5):203-11, 2001
Yeaman, G.R., Collins, J.E.; Fanger, M.W., Wira, C.R., Lydyard, P.L. CD8+ T cells in human uterine endometrial lymphoid aggregates: evidence for accumulation of cells by trafficking. Immunology 102(4):434-40, 2001
White, H.D., Musey, L., Andrews, M.M., Yeaman, G.R., DeMars, L.R., Manganiello, P.D., Howell, A.L., Wira, C.R., McElrath, M.J., and Green, W.R. HIV-Specific and CD3-redirected cytotoxic T lymphocyte activity in human female reproductive tract tissues: Lack of correlation between mucosa and peripheral blood. J. Infect. Diseases 183, 977-983 , 2001.
Fahey, J.V. and Wira, C.R. Effect of menstrual status on antibacterial activity and secretory leukocyte protease inhibitor production on human uterine epithelial cells in culture. J. Infect. Diseases 185:1606-1613, 2002.
Wira, C.R., Fahey, J.V., White, H.D., Yeaman, G.R., Givan, A.L. and Howell, A.L. The Mucosal Immune System in the Human Female Reproductive Tract: Influence of Stage of the Menstrual Cycle and Menopause on Mucosal Immunity in the Uterus. In: Endometrium. (Glasser, S., Aplin, J., Giudice, L. and Tabibzadeh, S., eds) Chapter 26, 2002, pages 371-404.
Wira, C.R. and Rossoll, R M. Estradiol regulation of antigen presentation by uterine stromal cells: Role of TGFb production by epithelial cells in mediating antigen presenting cell function. Immunol. 109:398-406, 2003
Grant, K.S. and Wira, C.R. Effect of mouse uterine stromal cells on epithelial cell transepithelial resistance (TER) and TNFa AND TGFb release in culture. Biol. Reprod. 69, 1091–1098, 2003.
Asin, S.N., Wildt-Perinic, D, Mason, S.I., Howell, A.L., Wira, C.R., and Fanger, M.W. Human immunodeficiency virus type 1 infection of human uterine epithelial cells: Viral shedding and cell contact-mediated infectivity. J. Infect. Diseases 187, 1522-1533, 2003.
Wira, C.R., Fahey, J.V., Abrahams V.M. and Rossoll, R.M. Influence of stage of the reproductive cycle and estradiol on thymus cell antigen presentation. J. Steroid Biochem. Mol. Biol. 84, 79-87, 2003.
Wira, C.R., Crane-Godreau, M. and Grant, K. Role of sex hormones and cytokines in regulating the mucosal immune system in the female reproductive tract. In: Mucosal Immunology. (Mestecky, J., Bienenstock, J., Lamm,
M.E., Mayer, L., McGhee, J.R. and Strober, W., eds.) Academic Press, NY, In Press, 2004.
Kutteh, W.H., Mestecky, J. and Wira, C.R. Chapter 90 Mucosal Immunity in the Human Female Reproductive Tract In: Mucosal Immunology. (Mestecky, J., Bienenstock, J., Lamm, M.E., Mayer, L., McGhee, J.R. and Strober, W., Eds.) Academic Press, NY, In Press, 2004.
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