Premium
Role of chemokines in lymphocyte trafficking to the intestine in chronic murine ileitis
Author(s) -
Schwartz Marc Andre,
RiveraNieves Jesus,
Ley Klaus
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a203
Subject(s) - ileitis , chemokine receptor , inflammation , c c chemokine receptor type 6 , immunology , c c chemokine receptor type 7 , chemokine , cxcr3 , ccr2 , ccl25 , cxc chemokine receptors , colitis , addressin , ccl20 , inflammatory bowel disease , receptor , biology , medicine , disease , crohn's disease , integrin
The recirculating lymphocytes responsible for maintaining chronic inflammation in Crohn’s disease traffic to the small intestine using an array of adhesion molecules and chemokines. Tissue‐specific trafficking to the intestine under normal physiologic conditions is controlled by the integrin α 4 β 7 and the chemokine receptor CCR9 expressed on lymphocytes recognizing their ligands MAdCAM‐1 and CCL25 (TECK), respectively, on endothelial cells in the intestinal microvasculature. We investigated the role of several chemokine receptors in the pathogenesis of chronic murine ileitis using RT‐PCR. At 10 weeks of age, when inflammation has developed but has not yet reached peak severity, expression of CCR6 and CCR7 in ilea was found to be 2‐fold and 4‐fold higher, respectively, in mice with ileitis relative to age‐matched controls. By 40 weeks, when chronic inflammation is well‐established, CCR7 showed no further increase in expression, but CCR6 expression had increased to 10‐fold greater than controls. CCR2, CCR5, CXCR2, CXCR3, and CXCR4 were also expressed at higher levels in mice with ileitis at 40 weeks. These data suggest that lymphocytes in mice with well‐established inflammation produce several inflammatory chemokine receptors that contribute to ileitis, but disease initiation involves dysregulation of a smaller set of tissue‐specific recruitment pathways. This work was supported by NIH grant DK 57880