Important role of CCR2 in a murine model of coronary vasculitis
<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 vasculiti...
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doaj-c0d4c380f57a4fd48dbe851f37e8719e2020-11-25T03:12:12ZengBMCBMC Immunology1471-21722012-10-011315610.1186/1471-2172-13-56Important role of CCR2 in a murine model of coronary vasculitisMartinez Hernan GQuinones Marlon PJimenez FabioEstrada CarlosClark Kassandra MSuzuki KazuoMiura NorikoOhno NaohitoAhuja Sunil KAhuja Seema S<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> http://www.biomedcentral.com/1471-2172/13/56CCR2Coronary vasculitisTregTreg/Th17 imbalance |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Martinez Hernan G Quinones Marlon P Jimenez Fabio Estrada Carlos Clark Kassandra M Suzuki Kazuo Miura Noriko Ohno Naohito Ahuja Sunil K Ahuja Seema S |
spellingShingle |
Martinez Hernan G Quinones Marlon P Jimenez Fabio Estrada Carlos Clark Kassandra M Suzuki Kazuo Miura Noriko Ohno Naohito Ahuja Sunil K Ahuja Seema S Important role of CCR2 in a murine model of coronary vasculitis BMC Immunology CCR2 Coronary vasculitis Treg Treg/Th17 imbalance |
author_facet |
Martinez Hernan G Quinones Marlon P Jimenez Fabio Estrada Carlos Clark Kassandra M Suzuki Kazuo Miura Noriko Ohno Naohito Ahuja Sunil K Ahuja Seema S |
author_sort |
Martinez Hernan G |
title |
Important role of CCR2 in a murine model of coronary vasculitis |
title_short |
Important role of CCR2 in a murine model of coronary vasculitis |
title_full |
Important role of CCR2 in a murine model of coronary vasculitis |
title_fullStr |
Important role of CCR2 in a murine model of coronary vasculitis |
title_full_unstemmed |
Important role of CCR2 in a murine model of coronary vasculitis |
title_sort |
important role of ccr2 in a murine model of coronary vasculitis |
publisher |
BMC |
series |
BMC Immunology |
issn |
1471-2172 |
publishDate |
2012-10-01 |
description |
<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> |
topic |
CCR2 Coronary vasculitis Treg Treg/Th17 imbalance |
url |
http://www.biomedcentral.com/1471-2172/13/56 |
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