Increased GM-CSF-producing NCR^- ILC3s and neutrophils in the intestinal mucosa exacerbate inflammatory bowel disease.

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.

SUBMITTER: Chang Y 

PROVIDER: S-EPMC8264747 | biostudies-literature |

REPOSITORIES: biostudies-literature