Overexpression of CXC chemokine ligand 14 exacerbates collagen-induced arthritis.
CXCL14 is a relatively new chemokine with unidentified receptor and undefined function. Recently, we found that CXCL14 is upregulated in arthritic joints in a mouse model of autoimmune arthritis, collagen-induced arthritis. To examine the role of CXCL14 in the development and pathogenesis of autoimmune arthritis, we have generated transgenic (Tg) mice that overexpress CXCL14 under control of phosphoglycerate kinase promoter. The results showed that CXCL14-Tg mice developed more severe arthritis compared with wild-type controls. The draining lymph nodes of CXCL14-Tg mice were significantly enlarged and contained an increased number of activated T cells, particularly the CD44(+)CD62L(low) effector memory cells. In addition, T cells from CXCL14-Tg mice exhibited an enhanced proliferative response against collagen II and produced higher levels of IFN-gamma but not IL-4 or IL-17. CXCL14-Tg mice also had elevated levels of IgG2a autoantibodies. These findings indicated that CXCL14 plays an important role in the autoimmune arthritis, which may have an implication in understanding the pathogenic mechanisms of rheumatoid arthritis in humans and, ultimately, therapeutic interference.
Chen
Limo
L
Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Guo
Linjie
L
Tian
Jun
J
He
Hongxia
H
Marinova
Ekaterina
E
Zhang
Pumin
P
Zheng
Biao
B
Han
Shuhua
S
D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D001323:Autoantibodies / Q000096:biosynthesis / Q000502:physiology; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D002645:Chickens; D024043:Collagen Type II / Q000633:toxicity; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D018836:Inflammation Mediators / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D001323:Autoantibodies; C118056:CXCL14 protein, human; D019743:Chemokines, CXC; D024043:Collagen Type II; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D018836:Inflammation Mediators; D011993:Recombinant Fusion Proteins