Increased GM‐CSF‐producing NCR‐ ILC3s and neutrophils in the intestinal mucosa exacerbate inflammatory bowel disease. Issue 7 (8th July 2021)

• Record Type: Journal Article
• Authors: Chang, Yuna; Kim, Ju Whi; Yang, Siyoung; Chung, Doo Hyun; Ko, Jae Sung; Moon, Jin Soo; Kim, Hye Young
• Is Part Of: Clinical & translational immunology. Volume 10:Issue 7(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-07-08
• Subjects: granulocyte -- Inflammatory bowel diseases -- innate lymphoid cells -- macrophage colony‐stimulating factor -- neutrophils; Immunologic diseases -- Periodicals; Immunology -- Periodicals; Clinical medicine -- Periodicals; Immune System Diseases -- therapy; Immunotherapy; Immunologic Factors -- therapeutic use; Translational Medical Research; Molecular Targeted Therapy; Clinical medicine; Immunologic diseases; Immunology; Periodicals; Periodicals; Fulltext; Internet Resources; Periodicals; 616.079
• DOI: 10.1002/cti2.1311
• Languages: English
• ISSNs: 2050-0068

Abstract

Abstract: Objectives: Inflammatory bowel disease (IBD) is characterised by dysregulated mucosal immune responses associated with genetic, environmental and microbial factors. Recent therapies targeting key inflammatory mediators such as tumor necrosis factor (TNF)‐α emphasise the importance of innate immunity in the development of IBD. Methods: We examined the distribution of innate immune cells such as innate lymphoid cells (ILCs) and myeloid cells in the intestinal epithelium from children diagnosed as IBD and murine models of colitis induced by dextran sulphate sodium (DSS) or an anti‐CD40 antibodies. Results: We found an increased number of type 3 ILCs (ILC3s) that do not express the natural cytotoxicity receptor (NCR) and neutrophils, in both human IBD patients and colitis‐induced mice. A co‐culture experiment of neutrophils with NCR ‐ ILC3s revealed that NCR ‐ ILC3s stimulate neutrophils by producing granulocyte–macrophage colony‐stimulating factor (GM‐CSF). Furthermore, a blockade of GM‐CSF could inhibit the development of IBD by inhibiting neutrophil activity. Conclusion: The NCR ‐ ILC3: GM‐CSF: neutrophil axis could contribute to the development of IBD. Abstract : We showed type 3 innate lymphoid cells (ILC3s) that do not express natural cytotoxicity receptor (NCR), and neutrophils, are increased in the inflamed colons from both humans and mice. NCR ‐ ILC3s produce granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and, in turn, stimulate neutrophils. This NCR‐ ILC3s: GM‐CSF: neutrophil axis may be a critical innate aspect of inflammatory bowel disease.