Circulating CD26 is negatively associated with inflammation in human and experimental arthritis.
Dipeptidyl peptidase IV (DPPIV, CD26), a protease-cleaving N-terminal X-Pro dipeptide from selected proteins including some chemokines, is expressed both as a soluble form in plasma and on the cell surface of various immune and nonimmune cell types. To gain insights into the pathophysiological role of CD26 in arthritis, we explored DPPIV/CD26 expression during murine antigen-induced arthritis (AIA), an experimental model of arthritis. AIA induction led to reduced plasma DPPIV activity. In CD26-deficient mice, the severity of AIA was increased as assessed by enhanced technetium uptake and by increased histological parameters of inflammation (synovial thickness and exudate). We demonstrated that CD26 controls the in vivo half-life of the intact active form of the proinflammatory chemokine stromal cell-derived factor-1 (SDF-1). CD26-deficient mice exhibited increased levels of circulating active SDF-1, associated with increased numbers of SDF-1 receptor (CXCR4)-positive cells infiltrating arthritic joints. In a clinical study, plasma levels of DPPIV/CD26 from rheumatoid arthritis patients were significantly decreased when compared to those from osteoarthritis patients and inversely correlate with C-reactive protein levels. In conclusion, decreased circulating CD26 levels in arthritis may influence CD26-mediated regulation of the chemotactic SDF-1/CXCR4 axis.
Busso
Nathalie
N
Laboratoire de Rhumatologie, Centre Hospitalier Universitaire Vaudois, Nestlé 05-5029, 1011 Lausanne, Switzerland. nathalie.busso@chuv.hospvd.ch
Wagtmann
Nicolai
N
Herling
Christian
C
Chobaz-Péclat
Veronique
V
Bischof-Delaloye
Angelika
A
So
Alexander
A
Grouzmann
Eric
E
D000368:Aged; D000818:Animals; D001168:Arthritis / Q000097:blood*; D001169:Arthritis, Experimental / Q000097:blood*; D049109:Cell Proliferation; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D002633:Chemotaxis; D018819:Dipeptidyl Peptidase 4 / Q000097:blood* / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D019718:Receptors, CXCR4 / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D010455:Peptides; D019718:Receptors, CXCR4; D007371:Interferon-gamma; D018819:Dipeptidyl Peptidase 4