Resistin-like molecule β regulates innate colonic function: Barrier integrity and inflammation susceptibility

Background

Resistin-like molecule (RELM) β is a cysteine-rich cytokine expressed in the gastrointestinal tract and implicated in insulin resistance and gastrointestinal nematode immunity; however, its function primarily remains an enigma.

Objective

We sought to elucidate the function of RELM-β in the gastrointestinal tract.

Methods

We generated RELM-β gene–targeted mice and examined colonic epithelial barrier function, gene expression profiles, and susceptibility to acute colonic inflammation.

Results

We show that RELM-β is constitutively expressed in the colon by goblet cells and enterocytes and has a role in homeostasis, as assessed by alterations in colon mRNA transcripts and epithelial barrier function in the absence of RELM-β. Using acute colonic inflammatory models, we demonstrate that RELM-β has a central role in the regulation of susceptibility to colonic inflammation. Mechanistic studies identify that RELM-β regulates expression of type III regenerating gene (REG) (REG3β and γ), molecules known to influence nuclear factor κB signaling.

Conclusions

These data define a critical role for RELM-β in the maintenance of colonic barrier function and gastrointestinal innate immunity.

Clinical implications

These findings identify RELM-β as an important molecule in homeostatic gastrointestinal function and colonic inflammation, and as such, these results have implications for a variety of human inflammatory gastrointestinal conditions, including allergic gastroenteropathies.

Key words: Allergy, colitis, gastrointestinal, inflammatory, innate, IL-13, mucosal, resistin

Abbreviations used: DAI, Disease activity index, DSS, Dextran sodium sulfate, ES, Embryonic stem, FITC, Fluorescein isothiocyanate, FIZZ, Found in inflammatory zone, IBD, Inflammatory bowel disease, NF-κB, Nuclear factor κB, RELM, Resistin-like molecule, REG, Regenerating gene, TNBS, Trinitrobenzene sulfonate, WT, Wild-type