CD43 functions as an E‐selectin ligand for Th17 cells in vitro and is required for Th17 cell recruitment in vivo

Abstract

Th17 cells are recruited at sites of inflammation and participate in important cell‐mediated inflammatory reactions. Their interactions with the vascular endothelium are highly dependent on Endothelial selectin (E‐sel). We hypothesized that Th17 cells use preferentially different E‐sel ligands than Th1 cells. We used real‐time live video microscopy to study the interactions of Th17 cells from different E‐sel ligand deficient mice with E‐sel under flow conditions and blot rolling assays, and the air pouch and experimental autoimmune encephalomyelitis (EAE) models of inflammation. We report that Th17 cells express the E‐sel ligands CD44, PSGL‐1 and CD43. Interestingly, CD43 functions as an E‐sel ligand for Th17 cells in vitro in a unique way that does not require cooperation with PSGL‐1. In vivo, CD43‐/‐ Th17 cells were not recruited into the air pouch in response to TNF‐α or CCL20. Interestingly, CD43‐/‐ mice were partially protected from EAE, and had reduced recruitment of Th17 cells to the central nervous system. Our results demonstrate the relevance of CD43 as an E‐sel ligand for Th17 cells in vitro, and its role in Th17 cell recruitment to sites of inflammation in vivo. Our results suggest the possibility to target Th17 cell recruitment specifically during inflammation. Future studies will unveil alternative mechanisms by which CD43 regulates Th17 cell recruitment in vivo in the context of disease.