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CCR7 deficiency causes diarrhea associated with altered ion transport in colonocytes in the absence of overt colitis

Item Type:Article
Title:CCR7 deficiency causes diarrhea associated with altered ion transport in colonocytes in the absence of overt colitis
Creators Name:Schumann, M. and Winter, S. and Wichner, K. and May, C. and Kuehl, A.A. and Batra, A. and Siegmund, B. and Zeitz, M. and Schulzke, J.D. and Lipp, M. and Hoepken, U.E.
Abstract:The chemokine receptor CCR7 is a central regulator in the maintenance of cellular homeostasis of mucosal tissues. CCR7(-/-) mice develop autoimmune gastritis and exocrinopathy accompanied by the formation of mucosal tertiary lymphoid follicles. Here we found that CCR7-deficient mice frequently suffered from chronic diarrhea linked with increased gastrointestinal motility and the development of severe anorectal prolapse. Enhanced formation of intestinal lymphoid follicles was associated with an elevated proportion of activated colonic T cells and increased production of the cytokine interleukin (IL)-1beta. To uncover the pathomechanisms of diarrhea in CCR7(-/-) mice, colonic epithelial barrier and ion channel activities were analyzed in Ussing chambers. Although overt acute colitis was absent, CCR7 deficiency resulted in reduced electrogenic sodium absorption and colonic chloride secretion. As it is known that IL-1beta regulates epithelial sodium channel (ENaC) activity, these data imply a causal link between CCR7 expression, IL-1beta level, and Na(+) malabsorption owing to altered ENaC expression and diarrhea.
Keywords:Biological Markers, CCR7 Receptors, Chlorides, Colitis, Colon, Cystic Fibrosis Transmembrane Conductance Regulator, Diarrhea, Epithelial Sodium Channel, Immunoglobulin G, Immunoglobulin M, Inbred C57BL Mice, Interleukin-1beta, Intestinal Mucosa, Ion Transport, Knockout Mice, Lymphocyte Activation, Messenger RNA, Peyer's Patches, Rectal Prolapse, Regulatory T-Lymphocytes, Animals, Mice
Source:Mucosal Immunology
ISSN:1933-0219
Publisher:Nature Publishing Group (U.S.A.)
Volume:5
Number:4
Page Range:377-387
Date:July 2012
Official Publication:https://doi.org/10.1038/mi.2012.15
PubMed:View item in PubMed

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