July 17 (MON) 16:30 / Auditorium (1F), PBC Commensal microbes regulate food antigens-induced spontaneous IgE production by restraining T follicular helper cells July 17 (MON) 16:30 / Auditorium (1F), PBC Dr. Sung-Wook Hong AIM, IBS Immunoglobulin E (IgE) is one of key mediators for exerting allergic reactions. IgE production is mediated by IL-4 from Th2 cells emerged in type 2 immune response such as allergen sensitization and helminth infection. Antigen-bound IgE mediates degranulation of mast cells and basophils which bear high-affinity receptor for IgE. Inflammatory mediators released by degranulation of these cells cause allergic symptoms such as urticaria, edema and bronchoconstriction. Since these reactions can be occurred very acutely and systemically, it can be very fatal to host. For this reason, IgE is only produced in limited conditions and is rarely detected in normal serum. Interestingly, IgE production is regulated by commensal microbes. Serum IgE level was spontaneously elevated in germ-free (GF) mice and antibiotics (ABX)-treated mice which have no or low burden of microbes. Although a previous study nicely showed that diversity of colonized microbes at early stage can determine life-long IgE level, both specificity of IgE elevated in GF mice and underlying mechanism for IgE elevation in GF condition are not fully understood yet. Spontaneously elevated IgE found in GF mice depends on CD4 T cells which are generally responsible for immunity to foreign antigens. Thus, we tested the role of food antigens in IgE elevation of GF mice since food antigen is the only foreign antigen in GF condition. We found that elevated IgE in GF mice is produced in response to food antigens by modulating the presence of food antigens by feeding mice with antigen-free diet (AFD) which is a liquid elemental diet devoid of macromolecules. According to a result that food antigens induce IgE production, Th2 cells were generated in response to food antigens only in gut-associated lymphoid organs where host immune system exposed to intestinal antigens. Furthermore, a majority of food antigens-induced Th2 cells in GF mice was T follicular helper (Tfh) subset bearing PD-1 and CXCR5. As a report that Tfh cells are specialized for helping B cell immunity by localizing in B cell zone, IgE production in GF mice were also mediated mainly by IL-4-producing Tfh cells. Interestingly, among different types of foods, only particular food antigens generated these Tfh cells mediate IgE elevation. Furthermore, we found that commensal microbes, especially vancomycin-susceptible bacteria, suppress generation of food antigens-induced Tfh cells and production of IgE. Our study is a first report which reveals a mechanism for why IgE is elevated in the absence of commensal microbes and shows commensal microbes affect host immune responses to food antigens. This provides new understanding for how commensal microbes affect the incidence of allergy. Inquiry: Dr. Charles D. Surh (279-0650) or AIM Administrative Team (Tel.279-0641, E-mail: hisgrace99@ibs.re.kr)