Differentiation of type 17 MAIT cells in circulation contributes to the severity of sepsis

This study identified a higher proportion of circulating MAIT17 with expression of IL-17A and RORγt in sepsis patients. The proportion of MAIT17 was correlated with the severity of sepsis. Single-cell RNA sequencing (scRNA-seq) analysis revealed an enhanced expression of lactate dehydrogenase A (LDHA) in MAIT17 in sepsis patients. Cell-culture experiments demonstrated that Phosphoinositide 3-kinase (PI3K)-LDHA signaling was required for RORγt expression in MAIT17. Finally, the elevated levels of plasma IL-18 promoted the differentiation of circulating MAIT17 in sepsis. In summary, this study reveals a new role of circulating MAIT17 in promoting sepsis severity and suggests the PI3K-LDHA signaling as a driving force in MAIT17 responses.PMID:38599461 | DOI:10.1016/j.ajpath.2024.03.010

Source: The American Journal of Pathology - April 10, 2024 Category: Pathology Authors: Xinying Li Sicheng Fu Hao Cheng Min Ma Zijian Song Jun Li Shuang Wu Chong Zhang Xiaoxia Wang Maoyu Tang Xuexue Pu Qiang Ji Jinquan Liang Zhibin Zhao Heinrich K örner Bin Li Min Shao Hua Wang Source Type: research