gp130 blockade to NOD off Crohn’s disease

doi:10.1016/j.it.2021.05.007

Trends in Immunology

Volume 42, Issue 7, July 2021, Pages 551-553

https://doi.org/10.1016/j.it.2021.05.007 Get rights and content

In a recent publication, Nayar et al. uncover specific inflammatory cell populations associated with Crohn’s disease (CD) pathogenesis, and a gp130-STAT3 signaling axis linked to disease in anti-TNF antibody treatment-refractory patients. Therefore, gp130 blockade might represent a potential CD therapy approach, perhaps in conjunction with existing anti-TNF treatment regimes.

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Acknowledgments

This work was supported by grants from Canadian Institutes of Health Research to D.J.P. T.M. was supported by the American Association of Immunologists (AAI) Intersect Fellowship Program for Computational Scientists and Immunologists.

Declaration of interests

The authors declare no competing interest.

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There are more references available in the full text version of this article.

Cited by (2)

Gut microbial DL-endopeptidase alleviates Crohn's disease via the NOD2 pathway
2022, Cell Host and Microbe
Citation Excerpt :
For example, Ruminococcus gnavus produces an inflammatory polysaccharide and induces inflammatory cytokine (TNF-α) secretion by dendritic cells (Henke et al., 2019), Atopobium parvulum induces pancolitis in colitis-susceptible Il10-deficient mice through producing hydrogen sulfide (Mottawea et al., 2016), and adherent-invasive Escherichia coli regulates phagocytes to drive intestinal inflammation through metabolism of propanediol (Viladomiu et al., 2021). When NOD2 signaling is intact, it could help the host’s defense against these pathologic insults and restore gut homeostasis in multiple ways (Caruso et al., 2014; Ramanan et al., 2014; Mukherjee and Philpott, 2021). Nonetheless, when NOD2 signaling is compromised in patients with NOD2 mutations or low DL-endopeptidase activity, inflammation could occur.
The pattern-recognition receptor NOD2 senses bacterial muropeptides to regulate host immunity and maintain homeostasis. Loss-of-function mutations in NOD2 are associated with Crohn’s disease (CD), but how the variations in microbial factors influence NOD2 signaling and host pathology is elusive. We demonstrate that the Firmicutes peptidoglycan remodeling enzyme, DL-endopeptidase, increased the NOD2 ligand level in the gut and impacted colitis outcomes. Metagenomic analyses of global cohorts (n = 857) revealed that DL-endopeptidase gene abundance decreased globally in CD patients and negatively correlated with colitis. Fecal microbiota from CD patients with low DL-endopeptidase activity predisposed mice to colitis. Administering DL-endopeptidase, but not an active site mutant, alleviated colitis via the NOD2 pathway. Therapeutically restoring NOD2 ligands with a DL-endopeptidase-producing Lactobacillus salivarius strain or mifamurtide, a clinical analog of muramyl dipeptide, exerted potent anti-colitis effects. Our study suggests that the depletion of DL-endopeptidase contributes to CD pathogenesis through NOD2 signaling, providing a therapeutically modifiable target.
The NF-κB signaling system in the immunopathogenesis of inflammatory bowel disease
2024, Science Signaling

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Trends in Immunology

Spotlightgp130 blockade to NOD off Crohn’s disease

Section snippets

Acknowledgments

Declaration of interests

Microbes Infect.

Lancet

Immunity

The pathogenesis and clinical management of stricturing Crohn disease

Inflamm. Bowel Dis.

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gp130 blockade to NOD off Crohn’s disease