Dietary fiber and segmented filamentous bacteria support the development of intraepithelial CD4⁺CD8αα⁺ T cells via epithelial MHC-II

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B107
Abstract ID: 5462

Presenting Author:
Naomi C Rodriguez Marino , Graduate Student at Emory Univ. Sch. of Med.

Abstract:

Double positive intraepithelial lymphocytes (DP IEL) are microbiota induced CD4⁺CD8αα⁺ anti-inflammatory T cells that help maintain homeostasis in the small intestine. It is poorly understood how changes in dietary fiber intake impact intestinal immune cell development through changes in the microbiota. Here we show that a diet low fermentable fiber (LFF) impairs development of DP IELs. 16s rRNA sequencing of the microbiota of LFF mice showed that segmented filamentous bacteria (SFB) is reduced in these mice. SFB closely interacts with intestinal epithelial cells (IEC). Bulk RNA sequencing of IECs of LFF-fed mice revealed lower expression of MHCII. Colonizing mice with SFB restored DP IEL development and increased expression of IEC MHCII and ileal IFNγ. IEC-specific deletion of MHCII and complete deletion of IFNγ receptor impaired SFB’s ability to induce DP IELs. Using Rag1^-/- mice we show that T cell-derived IFNγ is dispensable for SFB-induced IEC MHCII expression and that type 1 innate lymphoid cells (ILC1) express higher IFNγ in response to SFB colonization. Depleting ILCs resulted in lower expression of IEC MHCII on SFB⁺Rag1^-/- mice. Finally, we demonstrate that inducing MHCII on IEC with recombinant IFNγ is sufficient to support DP IEL development in SFB^- mice. Together, these results show that SFB colonization supported by dietary fiber is required for DP IEL development by inducing IFNγ expression from ILC1s and consequently increasing MHCII expression on IECs.