Interleukin 13 alleviates traumatic brain injury by promoting pericyte autophagy.

Interleukin 13 (IL13), as a cytokine belonging to the chemokine family, exhibits multiple complex physiological effects. Previous studies have consistently observed its significant role in various types of neural injuries and neurodegenerative diseases, including traumatic brain injury (TBI), through immune modulation and influencing neuroinflammation. However, little is known about its other physiological effects following TBI. In this study, we discovered a previously unreported important effect of IL13. In mouse models of TBI, we found that IL13 can protect against the loss of pericytes in a dose-dependent manner, and this effect was validated in two in vitro injury models relevant to TBI involving pericytes. Neutralizing IL13 levels significantly reversed this protective effect, highlighting the importance of IL13 in protecting pericytes after TBI. Further, through transcriptome analysis combined with pharmacological methods, both in vivo and in vitro experiments revealed that IL13 exerts this protective effect by promoting pericytes autophagy, which is crucial for IL13-induced angiogenesis and neuroprotection after TBI. Additionally, our mechanistic studies revealed that IL13 exerts this protective effect by activating the sirtuin 1 (SIRT1)/the forkhead box O3 (FOXO3) autophagy pathway. This finding provides new insights into the investigation of novel regulatory mechanisms of IL13 in neural injuries and highlights the crucial role of pericytes in TBI.