Important role of CCR2 in a murine model of coronary vasculitis

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Abstract

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.Conclusion: 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. © 2012 Martinez et al.; licensee BioMed Central Ltd.

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Martinez, H. G., Quinones, M. P., Jimenez, F., Estrada, C., Clark, K. M., Suzuki, K., … Ahuja, S. S. (2012). Important role of CCR2 in a murine model of coronary vasculitis. BMC Immunology, 13. https://doi.org/10.1186/1471-2172-13-56

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