title: Pathological Type-2 Immune Response, Enhanced Tumor Growth, and Glucose Intolerance in Retnlβ (RELMβ) Null Mice: A Model of Intestinal Immune System Dysfunction in Disease Susceptibility.
abstract: Resistin, and its closely related homologs, the resistin-like molecules (RELMs) have been implicated in metabolic dysregulation, inflammation, and cancer. Specifically, RELMβ, expressed predominantly in the goblet cells in the colon, is released both apically and basolaterally, and is hence found in both the intestinal lumen in the mucosal layer as well as in the circulation. RELMβ has been linked to both the pathogenesis of colon cancer and type 2 diabetes. RELMβ plays a complex role in immune system regulation, and the impact of loss of function of RELMβ on colon cancer and metabolic regulation has not been fully elucidated. We therefore tested whether Retnlβ (mouse ortholog of human RETNLβ) null mice have an enhanced or reduced susceptibility for colon cancer as well as metabolic dysfunction. We found that the lack of RELMβ leads to increased colonic expression of T helper cell type-2 cytokines and IL-17, associated with a reduced ability to maintain intestinal homeostasis. This defect leads to an enhanced susceptibility to the development of inflammation, colorectal cancer, and glucose intolerance. In conclusion, the phenotype of the Retnlβ null mice unravels new aspects of inflammation-mediated diseases and strengthens the notion that a proper intestinal barrier function is essential to sustain a healthy phenotype.
authors.affiliation: Institute of Neuroscience and Physiology (Metabolic Physiology), Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; Touchstone Diabetes Center, Departments of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: iwa@neuro.gu.se.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Wernstedt Asterholm
authors.affiliation: Touchstone Diabetes Center, Departments of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Ja Young
authors.initials: JY
authors.lastname: Kim-Muller
authors.affiliation: Touchstone Diabetes Center, Departments of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Rutkowski
authors.affiliation: Touchstone Diabetes Center, Departments of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Clair
authors.initials: C
authors.lastname: Crewe
authors.affiliation: Touchstone Diabetes Center, Departments of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Caroline
authors.initials: C
authors.lastname: Tao
authors.affiliation: Touchstone Diabetes Center, Departments of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: philipp.scherer@utsouthwestern.edu.
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
mesh_terms: D000818:Animals; D003092:Colitis / Q000235:genetics / Q000276:immunology*; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology; D005434:Flow Cytometry; D006729:Hormones, Ectopic / Q000235:genetics / Q000276:immunology*; D036341:Intercellular Signaling Peptides and Proteins; D007422:Intestines / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer
chemical_list: D006729:Hormones, Ectopic; D036341:Intercellular Signaling Peptides and Proteins; C486522:Retnlb protein, mouse