Pathological Type-2 Immune Response, Enhanced Tumor Growth, and Glucose Intolerance in Retnl (RELM) Null Mice: A Model of Intestinal Immune System Dysfunction in Disease Susceptibility.
Academic Article
Overview
Research
Identity
Additional Document Info
Other
View All
Overview
abstract
Resistin, and its closely related homologs, the resistin-like molecules (RELMs) have been implicatedin metabolic dysregulation, inflammation, and cancer. Specifically, RELM, expressed predominantly in the goblet cells in the colon, is released both apically and basolaterally, and is hence found in both theintestinal lumen in the mucosal layer as well as in the circulation. RELMhas been linked to both the pathogenesis of colon cancer and type 2 diabetes. RELM playsa complex role in immune system regulation, and the impact of loss of function of RELMoncolon cancer and metabolic regulation has not been fully elucidated. We therefore testedwhether Retnl (mouse ortholog of human RETNL) null mice have an enhanced or reducedsusceptibility for colon cancer as well as metabolic dysfunction. We found that the lack of RELM 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 Retnl null mice unravels new aspects of inflammation-mediated diseases and strengthens the notion that a proper intestinal barrier function is essential tosustaina healthy phenotype.
