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

• Published in: Journal of allergy and clinical immunology Vol. 118; no. 1; pp. 257 - 268
• Main Authors: Hogan, Simon P., Seidu, Luqman, Blanchard, Carine, Groschwitz, Katherine, Mishra, Anil, Karow, Margaret L., Ahrens, Richard, Artis, David, Murphy, Andrew J., Valenzuela, David M., Yancopoulos, George D., Rothenberg, Marc E.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.07.2006; Elsevier
• Subjects: Allergy; Animals; Basic and Clinical Immunology; Biological and medical sciences; colitis; Colitis - etiology; Colon - physiology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; gastrointestinal; Hormones, Ectopic - physiology; IL-13; Immunopathology; inflammatory; innate; Interleukin-13 - physiology; Medical sciences; Mice; Mice, Inbred C57BL; mucosal; Pancreatitis-Associated Proteins; Permeability; Proteins - genetics; resistin; Allergy; colitis; FIZZ; DSS; inflammatory; innate; IBD; IL-13; TNBS; DAI; ES; gastrointestinal; NF-κB; FITC; RELM; REG; resistin; WT; mucosal; Immunopathology; Digestive system; Barrier function; Mucosa; Cytokine; Inflammation; Interleukin 13; Gastrointestinal; Immunology; Digestive diseases; Intestinal disease; Colitis; Colon
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2006.04.039

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. We sought to elucidate the function of RELM-β in the gastrointestinal tract. We generated RELM-β gene–targeted mice and examined colonic epithelial barrier function, gene expression profiles, and susceptibility to acute colonic inflammation. 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. These data define a critical role for RELM-β in the maintenance of colonic barrier function and gastrointestinal innate immunity. 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.