GM‐CSF‐producing CCR2+CCR6+ Th17 cells are pathogenic in dextran sodium sulfate‐induced colitis model in mice

• Published in: Genes to cells : devoted to molecular & cellular mechanisms 2023-04, Vol.28 (4), p.267-276
• Main Authors: Ariki, Shimpei, Ozaka, Sotaro, Sachi, Nozomi, Chalalai, Thanyakorn, Soga, Yasuhiro, Fukuda, Chiaki, Kagoshima, Yomei, Ekronarongchai, Supanuch, Mizukami, Kazuhiro, Kamiyama, Naganori, Murakami, Kazunari, Kobayashi, Takashi
• Format: Article
• Language: English
• Subjects: Animals; CC chemokine receptors; CCR2; CCR6; CCR6 protein; Chemokine receptors; Chemokines - adverse effects; Colitis; Colitis - chemically induced; Colitis - genetics; CRISPR; Dextran; Dextrans - adverse effects; GM‐CSF; Granulocyte-Macrophage Colony-Stimulating Factor - adverse effects; Helper cells; Inflammatory bowel disease; Inflammatory Bowel Diseases; Localization; Lymphocytes T; Mice; Mice, Inbred C57BL; Mice, Knockout; Pathogenesis; pathogenic Th17 cell; Phenotypes; Receptors, CCR2 - genetics; Receptors, CCR6 - genetics; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; Sodium sulfate; Th17 Cells - metabolism; Th17 Cells - pathology
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1111/gtc.13008

Although excessive immune responses by Th17 cells, a helper T cell subset, are implicated in the pathogenesis of inflammatory bowel disease (IBD), the mechanism by which its localization in an inflamed colon is regulated remains unclear. Chemokines and their receptors are involved in the pathogenesis of IBD, however, the relative significance of each receptor on Th17 cells remains unknown. We generated C–C motif chemokine receptor 2 (CCR2) knockout (KO) and CCR6 KO mice in the syngeneic background using the CRISPR/Cas9 system and found that the phenotypes of experimental colitis worsened in both mutant mice. Surprisingly, the phenotype of colitis in CCR2/CCR6‐double knockout (CCR2/6 DKO) mice was opposite to that of the single‐deficient mice, with significantly milder experimental colitis (p