TY - JOUR
T1 - IL-27R signaling controls myeloid cells accumulation and antigen-presentation in atherosclerosis
AU - Peshkova, Iuliia O.
AU - Fatkhullina, Aliia R.
AU - Mikulski, Zbigniew
AU - Ley, Klaus
AU - Koltsova, Ekaterina K.
N1 - Funding Information:
This work was supported NCI P30 Cancer Center Grant to FCCC; and by AHA SDG 13SDG14490059, WW Smith Charitable Trust, NIH R21 CA202396, and NIH R56 HL133669 grants to E.K.K.
Publisher Copyright:
© The Author(s) 2017.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Myeloid cells, key players in atherosclerosis, take up and present antigens, leading to systemic and local T cell activation. The recruitment and activation of immune cells to the aorta in atherosclerosis is regulated by adhesion molecules, chemokines and cytokines. IL-27R is an immunoregulatory signaling nod in autoimmune and infectious pathologies. IL-27R was shown to suppress T cells activation in atherosclerosis, however it's possible role in myeloid cell accumulation and activation is not understood. Here we demonstrate that Apoe-/- Il27ra-/- mice fed with "Western Diet" for 7 or 18 weeks developed significantly more atherosclerosis compared to Apoe-/- Il27ra+/- controls. Accelerated disease was driven by enhanced expression of adhesion molecules and chemokines causing the accumulation of immune cells. Myeloid cells produced more inflammatory cytokines and upregulated MHCII. Multiphoton microscopy revealed more efficient interactions between aortic myeloid cells and CD4+ T cells. Overall, we show that IL-27R signaling controls endothelial cells activation and myeloid cell recruitment at early and advanced stages of atherosclerosis. In the absence of IL-27R myeloid cells become hyperactivated, produce pro-inflammatory cytokines and act as more potent antigen presenting cells. Enhanced interactions between Il27ra-/- APC and CD4+ T cells in the aortic wall contribute to T cells re-activation and pro-atherogenic cytokine production.
AB - Myeloid cells, key players in atherosclerosis, take up and present antigens, leading to systemic and local T cell activation. The recruitment and activation of immune cells to the aorta in atherosclerosis is regulated by adhesion molecules, chemokines and cytokines. IL-27R is an immunoregulatory signaling nod in autoimmune and infectious pathologies. IL-27R was shown to suppress T cells activation in atherosclerosis, however it's possible role in myeloid cell accumulation and activation is not understood. Here we demonstrate that Apoe-/- Il27ra-/- mice fed with "Western Diet" for 7 or 18 weeks developed significantly more atherosclerosis compared to Apoe-/- Il27ra+/- controls. Accelerated disease was driven by enhanced expression of adhesion molecules and chemokines causing the accumulation of immune cells. Myeloid cells produced more inflammatory cytokines and upregulated MHCII. Multiphoton microscopy revealed more efficient interactions between aortic myeloid cells and CD4+ T cells. Overall, we show that IL-27R signaling controls endothelial cells activation and myeloid cell recruitment at early and advanced stages of atherosclerosis. In the absence of IL-27R myeloid cells become hyperactivated, produce pro-inflammatory cytokines and act as more potent antigen presenting cells. Enhanced interactions between Il27ra-/- APC and CD4+ T cells in the aortic wall contribute to T cells re-activation and pro-atherogenic cytokine production.
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U2 - 10.1038/s41598-017-01828-8
DO - 10.1038/s41598-017-01828-8
M3 - Article
C2 - 28536468
AN - SCOPUS:85019574685
SN - 2045-2322
VL - 7
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 2255
ER -