Important role of CCR2 in a murine model of coronary vasculitis.
BACKGROUND
Chemokines and their receptors play a role in the innate immune response as well as in the disruption of the balance between pro-inflammatory Th17 cells and regulatory T cells (Treg), underlying the pathogenesis of coronary vasculitis in Kawasaki disease (KD).


RESULTS
Here we show that genetic inactivation of chemokine receptor (CCR)-2 is protective against the induction of aortic and coronary vasculitis following injection of Candida albicans water-soluble cell wall extracts (CAWS). Mechanistically, both T and B cells were required for the induction of vasculitis, a role that was directly modulated by CCR2. CAWS administration promoted mobilization of CCR2-dependent inflammatory monocytes (iMo) from the bone marrow (BM) to the periphery as well as production of IL-6. IL-6 was likely to contribute to the depletion of Treg and expansion of Th17 cells in CAWS-injected Ccr2(+/+) mice, processes that were ameliorated following the genetic inactivation of CCR2.


CONCLUSIONS
Collectively, our findings provide novel insights into the role of CCR2 in the pathogenesis of vasculitis as seen in KD and highlight novel therapeutic targets, specifically for individuals resistant to first-line treatments.
Department of Medicine (MC 7870), University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Hernan G
HG
Martinez
Marlon P
MP
Quinones
Fabio
F
Jimenez
Carlos
C
Estrada
Kassandra M
KM
Clark
Kazuo
K
Suzuki
Noriko
N
Miura
Naohito
N
Ohno
Sunil K
SK
Ahuja
Seema S
SS
Ahuja
D000818:Animals; D001011:Aorta / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology; D001854:Bone Marrow Cells / Q000473:pathology; D002176:Candida albicans / Q000166:cytology / Q000502:physiology; D002465:Cell Movement; D049109:Cell Proliferation; D002473:Cell Wall / Q000378:metabolism; D003331:Coronary Vessels / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D007109:Immunity / Q000276:immunology; D007249:Inflammation / Q000150:complications / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D008212:Lymphocyte Depletion; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000473:pathology; D009195:Peroxidase / Q000097:blood; D054390:Receptors, CCR2 / Q000172:deficiency / Q000378:metabolism*; D019713:Receptors, CCR5 / Q000172:deficiency / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology; D014657:Vasculitis / Q000097:blood / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control
C515335:Ccr2 protein, mouse; D015850:Interleukin-6; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D009195:Peroxidase