The arthritis severity quantitative trait locus Cia7 regulates neutrophil migration into inflammatory sites.
Neutrophils are required for the development of arthritis in rodents, and are the predominant cell in the synovial fluid of active rheumatoid arthritis. We hypothesized that neutrophil migration into the inflammed joint is genetically regulated. In addition, this genetic regulation would be accounted for by one of the arthritis loci that we have previously identified in an intercross between arthritis-susceptible DA and arthritis-resistant ACI rats studied for collagen-induced arthritis. We used the synovial-like air pouch model injected with carrageenan, and tested DA, ACI, and four congenic strains. ACI exudates had a significantly lower number of neutrophils compared with DA. Transfer of DA alleles at Cia7 into the ACI background, as in ACI.DA(Cia7) congenics, was enough to increase exudate neutrophil numbers to levels identical to DA, and this locus accounted for the difference between parental strains. None of the other congenic intervals explained the differences in exudate neutrophil counts. In conclusion, we have identified a novel function for Cia7, and determined that it regulates neutrophil migration into a synovial-like inflammatory site. Our data revealed no intrinsic defect in neutrophil responses to chemotactic agents, and suggest that Cia7 regulates an as yet unidentified factor central to neutrophil recruitment into inflammed tissues.
Laragione
T
T
1Laboratory of Experimental Rheumatology, The Robert S Boas Center for Genomics and Human Genetics, The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA.
Brenner
M
M
Yarlett
N C
NC
Mello
A
A
Miller
E J
EJ
Metz
C N
CN
Sherry
B
B
Gulko
P S
PS
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology*; D002351:Carrageenan; D002465:Cell Movement / Q000502:physiology*; D018925:Chemokines / Q000235:genetics; D002633:Chemotaxis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D009504:Neutrophils / Q000502:physiology*; D040641:Quantitative Trait Loci / Q000235:genetics*; D051381:Rats; D011912:Rats, Inbred ACI; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D013582:Synovial Fluid / Q000276:immunology / Q000378:metabolism*
D018925:Chemokines; D002351:Carrageenan