Blockade of CXCL10 protects mice from acute colitis and enhances crypt cell survival.
Crypt cell renewal is essential for normal intestinal homeostasis as well as mucosal regeneration following injury. However, the factors regulating crypt cell growth in pathological conditions are not fully understood. We report here that the endogenously produced chemokine CXCL10 regulates crypt cell proliferation. CXCL10 was constitutively expressed by basal crypts in mouse colon, but the expression of CXCL10 as well as CXCR3 was enhanced in the epithelium in the proliferative zone after oral administration of dextran sulfate sodium. Neutralization of CXCL10 protected mice from epithelial ulceration by promoting crypt cell survival without evidence of altered immune cell infiltration. Furthermore, recombinant CXCL10 administration into mice inhibited intestinal epithelial cell proliferation. These findings suggest that CXCL10 regulates crypt cell growth to maintain intestinal homeostasis in an autocrine or paracrine fashion. Thus, CXCL10 can be a new therapeutic target for inflammatory bowel disease by controlling the dynamics of epithelial homeostasis.
Sasaki
Shunya
S
Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Yoneyama
Hiroyuki
H
Suzuki
Kenji
K
Suriki
Hidehisa
H
Aiba
Tsuneo
T
Watanabe
Shiro
S
Kawauchi
Yusuke
Y
Kawachi
Hiroshi
H
Shimizu
Fujio
F
Matsushima
Kouji
K
Asakura
Hitoshi
H
Narumi
Shosaku
S
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors* / Q000502:physiology; D003093:Colitis, Ulcerative / Q000517:prevention & control*; D003106:Colon / Q000473:pathology*; D005260:Female; D007413:Intestinal Mucosa / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D011994:Recombinant Proteins