Epithelial CaSR deficiency alters intestinal integrity and promotes proinflammatory immune responses

Sam X. Cheng; Yaíma L. Lightfoot; Tao Yang; Mojgan Zadeh; Lieqi Tang; Bikash Sahay; Gary P. Wang; Jennifer L. Owen; Mansour Mohamadzadeh

doi:10.1016/j.febslet.2014.05.007

Epithelial CaSR deficiency alters intestinal integrity and promotes proinflammatory immune responses

Sam X. Cheng, Yaíma L. Lightfoot, Tao Yang, Mojgan Zadeh, Lieqi Tang, Bikash Sahay, Gary P. Wang, Jennifer L. Owen, Mansour Mohamadzadeh

Research output: Contribution to journal › Article › peer-review

68 Scopus citations

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.

Original language	English (US)
Pages (from-to)	4158-4166
Number of pages	9
Journal	FEBS Letters
Volume	588
Issue number	22
DOIs	https://doi.org/10.1016/j.febslet.2014.05.007
State	Published - Nov 17 2014
Externally published	Yes

Keywords

Calcium-sensing receptor
Colitis
Epithelial cell
Gut microbiota
Inflammation
Intestinal barrier function

ASJC Scopus subject areas

Genetics
Molecular Biology
Biophysics
Structural Biology
Biochemistry
Cell Biology

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10.1016/j.febslet.2014.05.007

Cite this

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title = "Epithelial CaSR deficiency alters intestinal integrity and promotes proinflammatory immune responses",

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.",

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T1 - Epithelial CaSR deficiency alters intestinal integrity and promotes proinflammatory immune responses

AU - Cheng, Sam X.

AU - Lightfoot, Yaíma L.

AU - Yang, Tao

AU - Zadeh, Mojgan

AU - Tang, Lieqi

AU - Sahay, Bikash

AU - Wang, Gary P.

AU - Owen, Jennifer L.

AU - Mohamadzadeh, Mansour

PY - 2014/11/17

Y1 - 2014/11/17

N2 - 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.

AB - 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.

KW - Calcium-sensing receptor

KW - Colitis

KW - Epithelial cell

KW - Gut microbiota

KW - Inflammation

KW - Intestinal barrier function

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Epithelial CaSR deficiency alters intestinal integrity and promotes proinflammatory immune responses

Abstract

Keywords

ASJC Scopus subject areas

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