Mucosal Immunology Unit
![A model of TGF-beta regulation of T cell immunity and tolerance in mucosal system](https://webarchive.library.unt.edu/eot2008/20090131062129im_/http://www.nidcr.nih.gov/NR/rdonlyres/5095CC9E-6D2D-4006-8801-D87ABD570D81/3178/ChenSlidefin.jpg) |
A model of TGF-beta regulation of T cell immunity and tolerance in mucosal system |
National Institutes of Health/ NIDCR
Building 30, Room 304
30 Convent Drive, MSC 4352
Bethesda, MD 20892-4352
Phone: (301) 435-7168
Fax: (301) 402-1064
E-mail: wchen@mail.nih.gov
Research Interests
The mucosae are the major ports of entry for foreign antigens. To deal with this challenge, more than 60% of our peripheral lymphoid tissue is deployed at the gut mucosa. Yet, not all foreign antigens are noxious or infectious pathogens. More than 100 kilograms of food antigens are processed each year by our gastrointestinal mucosa. Therefore, the gut immune system has to differentiate between beneficial dietary antigens and noxious or infectious pathogens. Failure to tolerate dietary antigens may lead to intestinal hypersensitivity as exemplified by food-sensitive enteropathies, and failure to expel infectious pathogens may contribute to disease. Thus, understanding of the mucosal immune system remains instrumental in developing strategies such as mucosal vaccination to infection and therapeutic means to allergy, inflammation and autoimmune diseases.
During complex but well-orchestrated immune responses in the mucosal system, T cells play a pivotal role in both immunity and tolerance. Of the cytokines and factors that are produced in and influence mucosal T cell immunity and tolerance, Transforming Growth Factor-beta (TGF-beta) is prominent and maybe the most important (see Figure). Our research interest is to elucidate mechanisms of TGF-beta regulation of T cell immunity and tolerance, and to manipulate T cell immunity versus tolerance in animal models to develop potential therapy for relevant human diseases such as autoimmune diseases, cancer and infectious diseases, with special attention to NIDCR mission relevant diseases, such as Sjogren's syndrome, periodontal diseases, and oral and head and neck cancers.
Education
M.D. Qingdao University Medical School 1984
M.S. Shandong Medical University & Shandong Academy of Medical Sciences 1987
Recent Publications
Chen, W., Frank, M.E., Jin, W., Wahl, S.M. 2001. Release of TGF- by apoptotic T cells contributes to an immunosuppressive milieu. Immunity 14:715-725.
Chen, W., Jin, W.J., Lei, K., Hardegen, N., Li, L., Marinos, N., Wahl, S.M. 2003. Conversion of peripheral CD4+CD25- regulatory T cells by TGF- induction of transcription factor Foxp3. J. Exp. Med. 198:1875-1886.
Chen, W., Wahl, S.M. 2003. TGF-: the missing link in CD4+CD25+ regulatory T cell-mediated immunosuppression. Cytokine Growth Factor Rev. 14:85-89.
Liu, Y., Armanath, S., Chen, W. 2006. Requirement of CD28 signaling in homeostasis/survival of TGF- converted CD4+CD25+ Treg from thymic CD4+CD25- single T cells. Transplantation. 82:953-64.
Chen, W., 2006. Dendritic cells and CD4+CD25+ T regulatory cells: crosstalk between two professionals. Frontiers in Bioscience. 11:1160-70.
Nandula, S., Amarnath, S., Molinolo, A., Hall, B., Goldsmith, C.M., Zheng, C., Larsson, J., Sreenath, T., Chen, W., Karlsson, S., Baum, B.J., Kulkarni, A.B. 2007. Female mice are more susceptible to developing inflammatory disorders due to impaired TGF-signaling in salivary glands. Arthritis and Rheumatism. 56:1978-805.
Ehirchiou, D., Xiong, Y., Xu, G., Chen, W., Shi, Y., Zhang, L. 2007. CD11b facilitates the development of peripheral tolerance by suppressing TH17 differentiation. J. Exp. Med. 204:1519-24.
Amarnath, S., Dong, L., Li, J., Wu, Y., Chen, W. 2007. Endogenous TGF- activation by reactive oxygen species is key to Foxp3 induction in TCR stimulated and HIV-1 infected human CD4+CD25- T cell. Retroviology. 4:57.
Perruche, S., Zhang, P., Liu, Y., Saas, P., Bluestone, J.A., Chen, W. 2008. CD3-specific antibody induced immune tolerance involves TGF- production by phagocytes digesting apoptotic T cells. Nature Med. In press.
Liu, Y., Zhang, P., Li, J., Kulkani, A.B., Perruche, S., Chen, W. 2008. A critical function for TGF- signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells. Natural Immunol. In press.