Gender	Male
E-mail	yaozhong.ding@mssm.edu
Education and Training	Ph.D., The University of Michigan

Education and Training	Ph.D., The University of Michigan

Both helper CD4 and cytotoxic CD8 T cells play a critical role in host defense against viruses, intracellular microbes, and tumors. My main interests are cytokine signaling and transcriptional control of T effector development, to investigate how CD4 T cells committed to Th2 differentiation, and how CD8 T cells acquire cytolytic activities.

1. Th2 commitment
   It is known that while the presence of IL-4 at the time of CD4 T cell activation is pivotal to Th2 differentiation, the cellular and molecular mechanisms that guide early IL-4 production remain elusive. c-Maf, the cellular homolog of the avian viral oncogene v-maf, has been demonstrated to directly bind to and regulate IL-4 promoter and gene expression. However, the pathways and controlling elements directing initial c-Maf expression are not clear. We found that IL-6 uniquely regulates c-Maf expression during early T cell activation, and that this induction requires both IL-6 initiated signaling and TCR activation. We now investigate the roles of Stat3, NFAT and CREB in c-Maf regulation; examine the possible roles of TCR or IL-6 signals in regulating chromatin modification at the c-maf promoter and how they may affect Stat3, NFAT1, or CREB binding; how IL-6 induced early c-Maf may coordinate with Stat6 and GATA3 to activate the IL4 promoter; determine how early c-Maf expression in CD4 T cells regulates IL-4 and Th2 differentiation. This research is supported by the NIH through 12/31/2009.
2. CD8 effector development
   Acquiring cytolytic activity and secretion of IFNI3 and TNFI? by CD8 effector T cells represent critical steps in host immune responses. The T-box transcription factor T-bet, and its paralogue Eomes, play important roles in regulating IFNI3 and CTL activities in CD8 T cells. T-bet directly binds to the promoters of perforin and granzyme B, is required for optimal IFNI3 expression and CTL activities during LCMV infection, and dominant negative T-bet and dominant negative Eomes both abolish IFNI3 production and CTL function in CD8 T cells. Little is known about how T-bet and Eomes are regulated in CD8 T cells. In my current study, we have found that IL-12 is able to induce a Stat1 independent T-bet expression in CD8 T cells, and identified a novel distal regulatory region responsible for the differential responses to Stat4 in T-bet regulation between CD8 and CD4 T cells. We are now investigating how T-bet and Eomes may interact with each other, and to define their biological roles in CD8 effector development.

Ding Y, Qin L, Yang Q, Punch JD, Fox DA, Hochman PS, Bromberg JS. A novel murine model for the assessment of human CD2-related reagents in vivo. J Immunol 1996 Sep 1; 157(5): 1863-9.

Ding Y, Qin L, Kotenko SV, Pestka S, Bromberg JS. A single amino acid required for stimulatory function of cellular Interleukin-10. J Exp Med 2000 Jan 17; 191(2): 213-24.

Ding Y, Qin L, Zamarin D, Kotenko SV, Pestka S, Moore KW, Bromberg JS. Differential IL-10R1 expression plays critical role in IL-10 mediated immune regulation. J Immunol 2001 Dec 15; 167(12): 6884-92.

Ding Y, Fu S, Zamarin D, Bromberg JS. Interleukin ?"10. In: Thomas AW, Lotze MT, editors. The Cytokine Handbook. Fourth Edition Academic Press; 2003.

Ding Y, Chen D, Tarcsafalvi A, Su R, Qin L, Bromberg JS. The Suppressor of Cytokine Signaling SOCS1 inhibits IL-10 mediated immune responses. J Immunol 2003 Feb 1; 170(3): 1383-91.

Yang Y, Ochando J, Yopp A, Bromberg JS, Ding Y. IL-6 plays a unique role in initiating c-Maf expression during early stage of CD4 T cell activation. J Immunol 2005 Mar 1; 174(5): 2720-9.