BCAP, a TLR/IL1R signaling adapter, intrinsically regulates differentiation of T helper cells (P1159)

Abstract

Abstract T helper cells utilize IL18 and IL1 signals provided by myeloid cells to achieve optimal Th1 and Th17 effector capacities. The IL1 and IL18 receptors belong to a family of receptors including Toll-like receptors (TLRs). The TLR/IL1R family share signaling components and (with the exception of TLR3) depend on the adapter MyD88 for engagement of downstream pathways. Signals from the receptor to the adapter are transmitted through homotypic interaction of TIR (Toll-Interleukin-1 receptor) homology domains found in all TLR/IL1R family members and their adapters. We have previously shown that BCAP (B-cell adapter for PI3K) contains a functional TIR domain enabling its participation in the TLR signaling pathway. Importantly, BCAP plays an obligate role in linking TLRs to activation of phosphoinositide 3-kinase (PI3K). Because the TLR/IL1R family share signaling components, we hypothesized that BCAP may regulate T cell differentiation through IL1R family signaling. Indeed, we found that BCAP intrinsically regulated differentiation of naïve T cells towards Th1 and Th17 effector lineages by participation in the IL1R family signaling pathways. Further, BCAP intrinsically regulated T cell proliferation and survival. Our continued efforts will further explore the molecular and transcriptional mechanisms by which BCAP regulates T cell activation. Significantly, this work will increase the understanding of key signaling pathways involved in disease and inflammation.