Epithelial CaSR deficiency alters intestinal integrity and promotes proinflammatory immune responses. Issue 22 (17th May 2014)

• Record Type: Journal Article
• Authors: Cheng, Sam X.; Lightfoot, Yaíma L.; Yang, Tao; Zadeh, Mojgan; Tang, Lieqi; Sahay, Bikash; Wang, Gary P.; Owen, Jennifer L.; Mohamadzadeh, Mansour
• Is Part Of: FEBS letters. Volume 588:Issue 22(2014)
• Page Start: 4158
• Page End: 4166
• Publication Date: 2014-05-17
• Subjects: CaSR -- calcium-sensing receptor -- IBD -- inflammatory bowel disease -- DCs -- dendritic cells -- TJ -- tight junction -- AJ -- adherens junction -- PRRs -- pattern recognition receptors -- GI -- gastrointestinal -- DSS -- dextran sulfate sodium -- TEER -- transepithelial electrical resistance -- ISC -- short-circuit current -- GT -- trans-epithelial conductance -- LP -- lamina propria -- Tregs -- regulatory T cells -- PD1 -- programmed cell death 1 -- PTH -- parathyroid hormone -- TNFR1 -- tumor necrosis factor receptor 1 -- Inflammation -- Calcium-sensing receptor -- Epithelial cell -- Gut microbiota -- Intestinal barrier function -- Colitis; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2014.05.007
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : The intestinal epithelium is equipped with sensing receptor mechanisms that interact with luminal microorganisms and nutrients to regulate barrier function and gut immune responses, thereby maintaining intestinal homeostasis. Herein, we clarify the role of the extracellular calcium‐sensing receptor (CaSR) using intestinal epithelium‐specific Casr −/− mice. Epithelial CaSR deficiency diminished intestinal barrier function, altered microbiota composition, and skewed immune responses towards proinflammatory. Consequently, Casr −/− mice were significantly more prone to chemically induced intestinal inflammation resulting in colitis. Accordingly, CaSR represents a potential therapeutic target for autoinflammatory disorders, including inflammatory bowel diseases.