The role of Segmented Filamentous Bacteria and intestinal epithelial cells in the induction of IFNγ production by ILC1s 4270

Abstract Description Intestinal epithelial cells (IECs) serve as non-conventional antigen presenting cells contributing to the microbiota-immune system crosstalk. Epithelial expression of class II major histocompatibility complex (MHCII) is induced by IFNγ and requires the microbiota. We showed that Segmented Filamentous Bacteria (SFB), an epithelial adherent commensal, induces IFNγ production by innate lymphoid cells type 1 (ILC1s) to upregulate IEC MHCII expression and facilitate the development of small intestinal intraepithelial T cells. However, the mechanism by which SFB and IECs induce IFNγ production by ILC1s is poorly understood. To address this gap, we performed bulk RNA sequencing on IECs of IFNγR-/- mice to identify IFNγ independent genes upregulated by SFB colonization. We found that IECs from SFB+IFNγR-/- mice have higher expression of toll-like receptor (TLR) 2. Nonetheless, TLR2-/- mice colonized with SFB have comparable expression of IEC MHCII as SFB+ WT mice. RNAseq analysis also revealed increased expression of IL-18, a known inducer of IFNγ that can be synthesized in response to TLR signaling. Using qPCR we confirmed that SFB colonization increases IL-18 expression in the ileum of WT mice. Furthermore, deletion of TLR signaling via MyD88 impairs SFB-induced expression of MHCII. Collectively, these results suggest that SFB sensing by IEC via TLRs contributes to the upregulation of MHCII and that epithelial derived IL-18 may play a role in inducing ILC1 IFNγ production. Funding Sources Supported by NIH 1R01DK129950 Topic Categories Mucosal and Regional Immunology (MUC)