Segmented Filamentous Bacteria Antigens Presented by Intestinal Dendritic Cells Drive Mucosal Th17 Cell Differentiation

Yoshiyuki Goto, Casandra Panea, Gaku Nakato, Anna Cebula, Carolyn Lee, Marta Galan Diez, Terri M. Laufer, Leszek Ignatowicz, and Ivaylo I. Ivanov.

Immunity. 2014 Apr 17;40(4):594-607. doi: 10.1016/j.immuni.2014.03.005. Epub 2014 Mar 27.

From left to right: Casandra Panea, Ivaylo I. Ivanov, Yoshiuki Goto

From left to right: Casandra Panea, Ivaylo I. Ivanov, Yoshiuki Goto

How commensal bacteria modulate mucosal T cell responses remains poorly understood. This study examines the     mechanisms of Th17 cell induction by segmented filamentous bacteria (SFB), which are potent and specific inducers of pro-inflammatory Th17 cells. The results show that recognition and presentation of SFB-derived antigens in the context of MHCII plays central role in Th17 cell induction. Almost all SFB-induced Th17 cells recognize SFB antigens, while at the same time non-Th17 mucosal CD4 T cells do not respond to SFB. Presentation of SFB antigens by intestinal MHCII+CD11c+ cells is necessary and sufficient for Th17 cell induction. Th17 cell priming and differentiation in response to SFB occurs in the small intestinal lamina propria and does not require organized secondary lymphoid organs, e.g. Peyer’s Patches or mesenteric lymph nodes. Therefore, commensal-specific Th17 cell responses can be induced in the lamina propria by intestinal dendritic cells. Interestingly, ablation of MHCII-expression on type 3 innate lymphoid cells (ILCs) resulted in an increase of Th17 cells in SFB-negative mice, demonstrating that ILCs curb Th17 cell responses at steady state. This study underscores the complex interplay between microbiota and innate immune cell subsets in modulating intestinal effector T cell responses. PMID: 24684957