| Summary: | <p>Abstract</p> <p>Background</p> <p>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).</p> <p>Results</p> <p>Here we show that genetic inactivation of chemokine receptor (CCR)-2 is protective against the induction of aortic and coronary vasculitis following injection of <it>Candida albicans</it> 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 <it>Ccr2</it><sup><it>+/+</it></sup> mice, processes that were ameliorated following the genetic inactivation of CCR2.</p> <p>Conclusion</p> <p>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.</p>
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