Reparative System Arising from CCR2(+) Monocyte Conversion Attenuates Neuroinflammation Following Ischemic Stroke
Joohyun Park, Jong Youl Kim, Yu Rim Kim, Meiying Huang, Ji Young Chang, Adelene Y. L. Sim, Hosung Jung, Won Taek Lee, Young‐Min Hyun, Jong Eun Lee
Abstract
Abstract Monocytes recruitment from the blood to inflamed tissues following ischemic stroke is an important immune response to wound healing and tissue repair. Mouse monocytes can be endogenously divided into two distinct populations: pro-inflammatory or classical monocytes that express CCR2 high CX3CR1 low and circulate in blood, and anti-inflammatory or non-classical monocytes that express CCR2 low CX3CR1 high and patrol locally. In this study of transgenic mice with functional CX3CR1 GFP/+ or CX3CR1 GFP/+ -CCR2 RFP/+ , we found that CCR2 high CX3CR1 low monocytes recruited to the injured brain were cytokine-dependently converted into CCR2 low CX3CR1 high macrophages, especially under the influence of IL-4 and IL-13, thereby attenuating the neuroinflammation following sterile ischemic stroke. The overall data suggest that (1) the regulation of monocyte-switching is one of the ultimate reparative strategies in ischemic stroke, and (2) the adaptation of monocytes in a locally inflamed milieu is vital to alleviating the effects of ischemic stroke through innate immunity.