Increased levels of chemokine receptor CXCR3 and chemokines IP-10 and MIG in patients with primary biliary cirrhosis and their first degree relatives.
Infiltrating memory T cells play an important role in the destruction of the biliary tract in primary biliary cirrhosis (PBC) and inflammatory chemokines control lymphocyte traffic through their interactions with T cell chemokine receptors. In the present study, we measured plasma levels of chemokines interferon-gamma-inducible protein-10 (IP-10) and monokine induced by gamma interferon (MIG), and also studied the expression of CXCR3 chemokine receptors in 105 subjects, including 53 patients with PBC, 26 first degree relatives and 26 healthy controls. Interestingly, plasma IP-10 and MIG levels in PBC were increased significantly compared to controls and appeared to increase with disease progression. By immunohistochemistry, IP-10 and MIG expressions were evident in the portal areas in PBC. Further, the frequency of CXCR3-expressing cells in peripheral blood was also significantly higher in PBC, and CXCR3-positive cells were also found in the portal areas of diseased livers, primarily on CD4+ cells. Finally, the daughters and sisters of PBC patients also demonstrated increased plasma levels of IP-10 and MIG, but, in contrast, displayed normal frequency of CXCR3+ expressing peripheral blood lymphocytes. Our data imply a role for specific chemokine-chemokine receptor interactions in the pathogenesis of PBC and also highlight the familial risk factor.
Chuang
Ya-Hui
YH
Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, 451 E. Health Sciences Drive, Suite 6510, Davis, CA 95616, USA.
Lian
Zhe-Xiong
ZX
Cheng
Chun-Mei
CM
Lan
Ruth Y
RY
Yang
Guo-Xiang
GX
Moritoki
Yuki
Y
Chiang
Bor-Luen
BL
Ansari
Aftab A
AA
Tsuneyama
Koichi
K
Coppel
Ross L
RL
Gershwin
M Eric
ME
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D054357:Chemokine CXCL10 / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D054370:Chemokine CXCL9 / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D054367:Receptors, CXCR3 / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D012307:Risk Factors; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
C114753:CXCL10 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D054367:Receptors, CXCR3