Cheong-Hee Chang, Ph.D.
Professor
Microbiology and Immunology
http://www.med.umich.edu/microbio/bio/chchang.htm

heechang@umich.edu

Current Research Activity:

Regulation of the effector function of CD4 T cells and dendritic cells

The research program in my laboratory has been focusing on investigating and understanding the molecular mechanisms that govern the adaptive immune function. Currently, two areas of research are ongoing: CD4 T cell development and effector function, and the cytokine network of dendritic cells.

It is believed that CD4 T cell generation requires MHC class II expressed in thymic epithelial cells (TEC). However, we have demonstrated that MHC class II expressing thymocytes are as efficient as TEC to support CD4 T cell development. Human thymocytes express MHC class II and our findings have provided a mechanism for several documented observations made in humans that could not be explained otherwise. Our recent studies show that the effector function of CD4 T cells is distinct depending on the thymic selection pathway. Unlike CD4 T cells selected on TEC, thymocyte-selected CD4 T cells produce both IL-4 and IFN- g immediately after in vivo as well as in vitro stimulation. Moreover, IL-4 is expressed in a Stat6-independent manner. These characteristics are found in NKT cells that are also selected on thymocytes. We are currently investigating how thymic selection programs the effector function of developing thymocytes, and the role of these CD4 T cells in immune responses.

The effector function of CD4 T cells is determined by the differentiation process in the periphery, which is controlled by antigen presenting cells (APC), particularly dendritic cells (DC). The major function of DC is to prime T cells by presenting antigens and producing effector cytokines. We have shown that these functions are regulated by multiple factors including the cytokine network in DC. The type and amount of cytokines produced by DC control the effector function of responding CD4 T cells, resulting in Th1 or Th2 immune response. Therefore, it is important to understand how the cytokine network is regulated in DC. We are studying DC function in the context of vaccinia virus infection and atopic dermatitis.

Selected publications:

Yongxue Yao, Wei Li, Mark Kaplan and Cheong-Hee Chang . IL-4 inhibits IL-10 to promote IL-2 production by dendritic cells. 2005. J. Exp. Med . 201:1899-1903. Highlighted in the same issue of JEM.

Wei Li, Moon G. Kim, Tania S. Gourley, Derek Sant'Angelo, and Cheong-Hee Chang. 2005. An Alternate Pathway for CD4 T cell Development: Thymocyte-Expressed MHC Class II Selects a Distinct T cell Population. Immunity. 23:375.

Li, P., N. Wang, D. Zhou, C.S.K. Yee, C-H. Chang , R. Brutkiewicz, and J.S. Blum. 2005. Disruption of MHC class II-restricted antigen presentation by vaccinia virus. J. Immunol. 175: 6481.

Zhao, Q., Wang, X., Nelin, L. D., Yao, Y., Manson, M. E., Baliga, R., Meng, X., Smith, C. V., Bauer, J. A., Chang, C.-H ., and Y. Liu. The role of MAP kinase phosphatase 1 in regulating LPS stimulated innate immune responses. 2006. J. Exp. Med. 203:131-40.

Yongxue Yao, Qi Xu, Myung-Ja Kwon, Ranyia Matta, Yusen Liu, Soon-Cheol Hong, and Cheong-Hee Chang. ERK and p38 MAPK signaling pathways negatively regulate CIITA gene expression in dendritic cells and macrophages. 2006. J. Immunol. 170:70-76.

Myung-Ja Kwon, Jae-Won Soh, and Cheong-Hee Chang . Protein Kinase C delta is essential to maintain CIITA gene expression in B cells. 2006. J. Immunol. 177:950-956.

Wei Li, Hanief Sofi, Norman Yeh, Dipak Patel, Randy Brutkiewicz, Mark Kaplan, and Cheong-Hee Chang. 2007. Thymic selection pathway regulates cytokine production potential of CD4 T cells. J. Exp Med. 2007 Sep 3;204(9):2145-57.