Crucial roles of XCR1-expressing dendritic cells and the XCR1-XCL1 chemokine axis in intestinal immune homeostasis

• DOI: 10.1038/srep23505
• Publication Date: 2016-03-23T10:17:32Z
• Authors: Tomokazu Ohta; Masanaka Sugiyama; Hiroaki Hemmi; Chihiro Yamazaki; Soichiro Okura; Izumi Sasaki; Yuri Fukuda; Takashi Orimo; Ken J. Ishii; Katsuaki Hoshino; Florent Ginhoux; Tsuneyasu Kaisho
• Keywords: T-Lymphocytes; immunology; Mice; 0302 clinical medicine; cell motion; Cell Movement; homeostasis; Receptors; T lymphocyte; Homeostasis; animal; Cells, Cultured; Xcl1 protein; Cultured; chemokine receptor; deficiency; gene expression regulation; 3. Good health; Intestines; Chemokine; Receptors, Chemokine; Chemokines; dendritic cell; Cell Survival; Cells; 610; cell survival; Article; 03 medical and health sciences; Cross-Priming; C; gene expression profiling; Animals; procedures; XC chemokine receptor 1; intestine; mouse; Cell Proliferation; cell culture; cross presentation; Gene Expression Profiling; Dendritic Cells; gamma chemokine; Chemokines, C; cell proliferation; Gene Expression Regulation; physiology; cytology; metabolism

AbstractIntestinal immune homeostasis requires dynamic crosstalk between innate and adaptive immune cells. Dendritic cells (DCs) exist as multiple phenotypically and functionally distinct sub-populations within tissues, where they initiate immune responses and promote homeostasis. In the gut, there exists a minor DC subset defined as CD103+CD11b− that also expresses the chemokine receptor XCR1. In other tissues, XCR1+ DCs cross-present antigen and contribute to immunity against viruses and cancer, however the roles of XCR1+ DCs and XCR1 in the intestine are unknown. We showed that mice lacking XCR1+ DCs are specifically deficient in intraepithelial and lamina propria (LP) T cell populations, with remaining T cells exhibiting an atypical phenotype and being prone to death and are also more susceptible to chemically-induced colitis. Mice deficient in either XCR1 or its ligand, XCL1, similarly possess diminished intestinal T cell populations and an accumulation of XCR1+ DCs in the gut. Combined with transcriptome and surface marker expression analysis, these observations lead us to hypothesise that T cell-derived XCL1 facilitates intestinal XCR1+ DC activation and migration and that XCR1+ DCs in turn provide support for T cell survival and function. Thus XCR1+ DCs and the XCR1/XCL1 chemokine axis have previously-unappreciated roles in intestinal immune homeostasis.