Epithelial CaSR deficiency alters intestinal integrity and promotes proinflammatory immune responses.
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.
Division of Gastroenterology, Department of Pediatrics, University of Florida, Gainesville, FL 32607, USA.
Sam X
SX
Cheng
Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL 32608, USA; Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine, University of Florida, Gainesville, FL 32610, USA.
Yaíma L
YL
Lightfoot
Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL 32608, USA; Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine, University of Florida, Gainesville, FL 32610, USA.
Tao
T
Yang
Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL 32608, USA; Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine, University of Florida, Gainesville, FL 32610, USA.
Mojgan
M
Zadeh
Division of Gastroenterology, Department of Pediatrics, University of Florida, Gainesville, FL 32607, USA.
Lieqi
L
Tang
Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL 32608, USA; Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine, University of Florida, Gainesville, FL 32610, USA.
Bikash
B
Sahay
Division of Infectious Diseases and Global Medicine, Department of Medicine, University of Florida, Gainesville, FL 32610, USA.
Gary P
GP
Wang
Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA.
Jennifer L
JL
Owen
Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL 32608, USA; Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine, University of Florida, Gainesville, FL 32610, USA. Electronic address: m.zadeh@ufl.edu.
Mansour
M
Mohamadzadeh
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D016264:Dextran Sulfate / Q000009:adverse effects; D055786:Gene Knockout Techniques; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000187:drug effects; D044169:Receptors, Calcium-Sensing / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D044169:Receptors, Calcium-Sensing; D016264:Dextran Sulfate
Calcium-sensing receptor; Colitis; Epithelial cell; Gut microbiota; Inflammation; Intestinal barrier function