The role of CCR5+ monocytes in DHCA-induced lung injury

Acute lung injury (ALI) is a common serious complication following deep hypothermic circulatory arrest (DHCA). Monocytes and macrophages play a crucial role in producing inflammatory mediators and regulating innate and adaptive immunity. In our specific rat model of DHCA‐induced ALI, We have previously shown that autophagy actually has a detrimental effect on lung injury rather than a protective effect. Recently, we found that monocytes have an important function in this model. Here, single-cell RNA sequencing was performed on the lung tissue cells collected from healthy rats, and rats after DHCA, notably, there was a selective and dramatic increase in the subpopulation of CD43 ^low monocytes in the DHCA group, which expressed high levels of CCR5 and exhibited a pro-inflammatory phenotype. Allosteric CCR5 drug blockade not only reduced CCR5 expression and alleviated lung injury, but interestingly also inhibited autophagy levels. These results suggest that the recruitment of CCR5 ⁺ inflammatory monocytes into pulmonary tissue contributes to ALI after DHCA, and blocking CCR5 is a plausible intervention for DHCA-induced lung injury by modulating autophagy levels.