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- Title
Increased GM‐CSF‐producing NCR<sup>‐</sup> ILC3s and neutrophils in the intestinal mucosa exacerbate inflammatory bowel disease.
- Authors
Chang, Yuna; Kim, Ju Whi; Yang, Siyoung; Chung, Doo Hyun; Ko, Jae Sung; Moon, Jin Soo; Kim, Hye Young
- 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.
- Subjects
INFLAMMATORY bowel diseases; INNATE lymphoid cells; INTESTINAL mucosa; MYELOID cells; INTESTINAL diseases; GRANULOCYTE-macrophage colony-stimulating factor
- Publication
Clinical & Translational Immunology, 2021, Vol 10, Issue 7, p1
- ISSN
2050-0068
- Publication type
Article
- DOI
10.1002/cti2.1311