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Dobesova, M.

Publications and source records attributed to Dobesova, M..

2 recordsLinked to original sources

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

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.

immunology↗

A model of preferential pairing between epithelial and dendritic cells in thymic antigen transfer

Medullary thymic epithelial cells (mTECs) which produce and present self-antigens are essential for the establishment of central tolerance. Since mTEC numbers are limited, their function is complemented by thymic dendritic cells (DCs), which transfer mTEC-produced self-antigens via cooperative antigen transfer (CAT). While CAT is required for effective T cell selection, many aspects remain enigmatic. Given the recently described heterogeneity of mTECs and DCs, it is unclear whether the antigen acquisition from a particular TEC subset is mediated by preferential pairing with specific subset of DCs. Using several relevant Cre-based mouse models controlling the expression of fluorescent proteins, we found that in regards to CAT, each subset of thymic DCs preferentially targets distinct mTEC subset(s) and importantly, XCR1+ activated DCs represented the most potent subset in CAT. Interestingly, one thymic DC can acquire antigen repetitively and of these, monocyte-derived DCs (moDC) were determined to be the most efficient in repetitive CAT. moDCs also represented the most potent DC subset in the acquisition of antigen from other DCs. These findings suggest a preferential pairing model for the distribution of mTEC-derived antigens among distinct populations of thymic DCs.

immunology↗