Essential role for CD103 in the T cell–mediated regulation of experimental colitis

Abstract

The integrin CD103 is highly expressed at mucosal sites, but its role in mucosal immune regulation remains poorly understood. We have analyzed the functional role of CD103 in intestinal immune regulation using the T cell transfer model of colitis. Our results show no mandatory role for CD103 expression on T cells for either the development or CD4+CD25+ regulatory T (T reg) cell–mediated control of colitis. However, wild-type CD4+CD25+ T cells were unable to prevent colitis in immune-deficient recipients lacking CD103, demonstrating a nonredundant functional role for CD103 on host cells in T reg cell–mediated intestinal immune regulation. Non–T cell expression of CD103 is restricted primarily to CD11chighMHC class IIhigh dendritic cells (DCs). This DC population is present at a high frequency in the gut-associated lymphoid tissue and appears to mediate a distinct functional role. Thus, CD103+ DCs, but not their CD103− counterparts, promoted expression of the gut-homing receptor CCR9 on T cells. Conversely, CD103− DCs promoted the differentiation of IFN-γ–producing T cells. Collectively, these data suggest that CD103+ and CD103− DCs represent functionally distinct subsets and that CD103 expression on DCs influences the balance between effector and regulatory T cell activity in the intestine.

Induction of organ‐selective CD4+ regulatory T cell homing

“…For example, T cells activated in mLN and PP draining the gut acquire high levels of the integrin a 4 b 7 , whereas activation in skin-draining peripheral LN (pLN) results in the upregulation of selectin ligands such as P-lig. Tissuespecific DC have been shown in a number of in vitro and in vivo studies to be involved in the instruction of naïve T cells [4,[17][18][19][20][22][23][24] reported that GALT DC were capable of converting metabolites of dietary vitamin A into retinoic acid (RA), which in turn induced T cell expression of a 4 b 7 and CCR9, leading to the generation of gut-tropic T cells. However, the factors, which are involved in the generation of skin-specific T cell homing in vivo, are largely unknown, although important roles for cytokines including IL-12 and TGF-b have been suggested from in vitro studies [26][27][28].…”

CD8+CD103+ Tumor–Infiltrating Lymphocytes Are Tumor-Specific Tissue-Resident Memory T Cells and a Prognostic Factor for Survival in Lung Cancer Patients

“…Indeed, the interaction of CD103 on tumor-specific tumorinfiltrating lymphocytes (TIL) with its ligand, E-cadherin on tumor cells, is necessary for positioning the cytotoxic granules near the interface and their delivery into the target, leading to lysis of the latter cells (3). CD103 is expressed at high levels by mucosal CD8 + T lymphocytes, in particular intestinal intraepithelial lymphocytes (4), but it is also found on mucosal mast cells and dendritic cells (5), CD4 + and CD8 + regulatory T cells (6), and on a large proportion of CD8 + T cells infiltrating epithelial tumors, including pancreatic (7), colorectal (8), lung (3), and ovarian cancers (9). It has been recently reported that CD103 expression on TIL is associated with increased survival in high-grade serous ovarian cancer (10).…”

MyD88 Signaling Regulates Steady-State Migration of Intestinal CD103+ Dendritic Cells Independently of TNF-α and the Gut Microbiota

“…We and others have identified a functional specialization of DCs in the gut-draining mesenteric LN (MLN) that express the integrin a-chain CD103 (9,10). These DCs display an enhanced ability to induce the gut-homing molecules CCR9 and a 4 b 7 on T cells and, in the presence of TGF-b, support the differentiation of Foxp3 + T regulatory (Treg) cells in vitro through mechanisms involving the vitamin A metabolite retinoic acid (RA) (9,11,12).…”