MHCII Expression by Intestinal Goblet Cells in Immune Homeostasis

Abstract

Abstract As the primary barrier in the gut, intestinal epithelial cells (IECs) are positioned to promote tolerance and immunity against pathogens. MHCII is highly expressed on IECs, however MHCII expression on epithelial cell subsets is largely unexplored. Goblet cells (GCs) are specialized epithelial cells that have critical role in barrier maintenance and immunity. GC can form Goblet cells associated passage (GAPs) and deliver luminal antigens to lamina propria (LP) antigen presenting cells (APC) to induce adaptive immune responses. Here, we report that MHCII is highly expressed on small intestinal GCs as compared with other IECs and colon IECs, which do not form GAPs in the steady state. Moreover, expression of coinhibitory and costimulatory molecules by GCs was higher when compared with other IECs. Interestingly, flow analysis and quantification of MHCII on CD45.2 +MHC-II −/−donor-derived leukocytes showed MHCII acquisition by donor-derived small intestinal lamina propria (siLP) APCs 7 weeks after BM-transplant into CD45.1 +recipients. Indeed, carbachol, which induces GAPs formation resulted in increased MHCII acquisition by CD45.2 +MHC-II −/−donor-derived siLP MNPs. Furthermore, selective deletion of MHCII on GCs, resulted in a significant reduction of transferred dietary antigen specific OT-II +CD45.1 +CD4 +T cells in mLN in a model of oral tolerance. Bulk RNAseq analysis on the small intestine of mice with GC deletion of MHCII revealed an expansion of B cell responses and significant increase in IgA+ cells in Peyer’s patches. This data suggests that GC expression of MHCII has a role in antigen-specific responses to luminal antigens and in regulating intestinal homeostasis. Supported by grants from NIH