Reparative System Arising from CCR2(+) Monocyte Conversion Attenuates Neuroinflammation Following Ischemic Stroke

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.

Automated summary

After ischemic stroke, CCR2(high)CX3CR1(low) monocytes recruited to the injured brain are cytokine-dependently converted into CCR2(low)CX3CR1(high) macrophages, attenuating neuroinflammation. The regulation of monocyte-switching is crucial in ischemic stroke, and the adaptation of monocytes in a locally inflamed milieu is vital in alleviating the effects of stroke through innate immunity.