Dataset Information

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 | 2021

REPOSITORIES: biostudies-literature

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Publications

Increased GM-CSF-producing NCR<sup>-</sup> ILC3s and neutrophils in the intestinal mucosa exacerbate inflammatory bowel disease.

Chang Yuna Y Kim Ju Whi JW Yang Siyoung S Chung Doo Hyun DH Ko Jae Sung JS Moon Jin Soo JS Kim Hye Young HY

Clinical & translational immunology 20210708 7

<h4>Objectives</h4>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.<h4>Methods</h4>We examined the distribution of innate immune cells such as innate lymphoid cells (ILCs) and myeloid cells in the intestinal epithelium from children ...[more]

PMID: 34262760

Similar Datasets

Project description:Given that granulocyte macrophage colony-stimulating factor (GM-CSF) is identified as the key factor to endow auto-reactive Th cells with the potential to induce neuroinflammation in experimental autoimmune encephalomyelitis (EAE) models, the frequency and phenotype of GM-CSF-producing (GM-CSF+) Th cells in draining lymph nodes (dLNs) and spinal cord (SC) of Albino Oxford (AO) and Dark Agouti (DA) rats immunized for EAE were examined. The generation of neuroantigen-specific GM-CSF+ Th lymphocytes was impaired in dLNs of AO rats (relatively resistant to EAE induction) compared with their DA counterparts (susceptible to EAE) reflecting impaired CD4+ lymphocyte proliferation and less supportive of GM-CSF+ Th cell differentiation dLN cytokine microenvironment. Immunophenotyping of GM-CSF+ Th cells showed their phenotypic heterogeneity in both strains and revealed lower frequency of IL-17+IFN-γ+, IL-17+IFN-γ-, and IL-17-IFN-γ+ cells accompanied by higher frequency of IL-17-IFN-γ- cells among them in AO than in DA rats. Compared with DA, in AO rats was also found (i) slightly lower surface density of CCR2 (drives accumulation of highly pathogenic GM-CSF+IFN-γ+ Th17 cells in SC) on GM-CSF+IFN-γ+ Th17 lymphocytes from dLNs, and (ii) diminished CCL2 mRNA expression in SC tissue, suggesting their impaired migration into the SC. Moreover, dLN and SC cytokine environments in AO rats were shown to be less supportive of GM-CSF+IFN-γ+ Th17 cell differentiation (judging by lower expression of mRNAs for IL-1β, IL-6 and IL-23/p19). In accordance with the (i) lower frequency of GM-CSF+ Th cells in dLNs and SC of AO rats and their lower GM-CSF production, and (ii) impaired CCL2 expression in the SC tissue, the proportion of proinflammatory monocytes among peripheral blood cells and their progeny (CD45hi cells) among the SC CD11b+ cells were reduced in AO compared with DA rats. Collectively, the results indicate that the strain specificities in efficacy of several mechanisms controlling (auto)reactive CD4+ lymphocyte expansion/differentiation into the cells with pathogenic phenotype and migration of the latter to the SC contribute to AO rat resistance to EAE.

Dataset Information

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

Objectives

Methods

Results

Conclusion

Publications

Increased GM-CSF-producing NCR<sup>-</sup> ILC3s and neutrophils in the intestinal mucosa exacerbate inflammatory bowel disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Objectives

Methods

Results

Conclusion

Publications

Increased GM-CSF-producing NCR<sup>-</sup> ILC3s and neutrophils in the intestinal mucosa exacerbate inflammatory bowel disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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