March 13(MON) 16:30 / Auditorium (1F), PBC Diet-induced IL-12 Stimulates Intraepithelial T cells to Defend Tentative Pathogens March 13(MON) 16:30 / Auditorium (1F), PBC Jisun Jung POSTECH Intraepithelial lymphocytes (IELs) are the biggest lymphocyte population in our body and ready to be cytotoxic in the proximity to epithelial cells. They are abundantly present in the small intestine and serve as the first line of defense against invading pathogens and to maintain homeostasis of the intestinal epithelial cells. However, what induces IEL cytotoxic differentiation is poorly understood. Although main function of the small intestine is to absorb the nutrition from diet, more attention has been focused on the influences of commensal microbiota on IELs. Hence, in order to investigate the role of both microbiota and diet in development and effector function of IELs, we compared subsets of IELs in the offspring of germ-free (GF) B6 mice raised with a chemically defined elemental diet. Apparently, in such “Ag-free” (AF) mice, conventional IELs, i.e., TCRαβ+CD4+, TCRαβ+CD4+CD8α+ IELs, TCRαβ+CD8αβ+, are severely depleted and unconventional TCRαβ+CD8αα+ IELs are partially depleted. The TCRγδ+CD8αα+ IEL population was relatively unaffected in AF mice compared to SPF or GF mice. More importantly, we found that the residual IELs as well as other subsets of IELs in the small intestine of AF mice, unlike those in SPF and GF mice, do not display constitutive effector function. Mechanistically, we found that IL-12 production is required for diet to induce and sustain normal Granzyme B expression in conventional IELs. Overall, we suggest that consumption of diet is important for normal generation of functional IELs to lead homeostasis of mucosal immune system. Hence, theses IELs reside as innate-like killing cells to protect us from tentative pathogens come along with diet. Inquiry: Dr. You Jeong Lee (279-2359) or AIM Administrative Team (Tel.279-0641, E-mail: hisgrace99@ibs.re.kr)