Epithelial antigen presentation controls commensal-specific intraepithelial T-cells in the gut

Abstract

The expression of MHCII by intestinal epithelial cells (IEC) determines the severity of intestinal immunopathological reactions. However, the function of MHCII on IEC under homeostatic conditions remains elusive. Here we report that MHCII expression on IECs is a hallmark of an adaptive wave of homeostatic intestinal immune responses to commensal segmented filamentous bacteria (SFB). Focusing on SFB-driven responses, we describe the expression pattern of MHCII and the associated antigen processing machinery among IEC subpopulations along with the cellular network that regulates MHCII induction. Furthermore, we show that SFB induce the accumulation of SFB-specific intraepithelial lymphocytes (IELs) that originate from conventional CD4+ T-cells. Importantly, induced IELs are dependent on the epithelial MHCII. Finally, we demonstrate that both epithelial MHCII and the IEL functionality regulate the epithelial turnover. This study describes the organization of a commensal-targeted, IEL-driven immune response that is controlled by IEC antigen presentation and ultimately regulates IEC turnover.

Selection of cross-reactive T cells by commensal and food-derived yeasts drives cytotoxic TH1 cell responses in Crohn’s disease

“…As healthy individuals also harbor commensal intestinal yeasts and frequently ingest S. cerevisiae in the diet, the observed altered T cell reactivity in patients with CD and the incipient changes in individual IBD-FDRs may reflect a more intense or sustained interaction with yeast antigens, owing to epithelial barrier dysfunction. T cell-mediated cytotoxicity has been described as contributing to IEC death 47,48 and exacerbated T H 1 immunity in mice promoted epithelial barrier defects and mucosal fungal infection 49 . It is therefore tempting to speculate that yeast-responsive T H -CTLs may be directly involved in disease initiation and/or exacerbation through disruption of the intestinal barrier.…”

Analysis of intestinal epithelial cell responses toCryptosporidiumhighlights the temporal effects of IFN-γ on parasite restriction

“…Since IEC express MHC-I and MHC-II, this is consistent with the idea that IFN-γ stimulation of IEC promotes cognate interactions between CD4 + and CD8 + T cells and epithelial cells required for parasite control (5). Indeed, a recent report highlighted that during infection with SFB, the ability of CD4 + T cells to promote IEC turnover was dependent on IEC expression of MHC-II (37). The ability to genetically modify Cryptosporidium to express model antigens (38) will likely facilitate similar studies in this system.…”