Am J Pathol. 2024 Apr 08. pii: S0002-9440(24)00125-1. [Epub ahead of print]
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 Körner,
Bin Li,
Min Shao,
Hua Wang.
Mucosal-associated invariant T (MAIT) cells are essential in defending against infection. Sepsis is a systemic inflammatory response to infection and a leading cause of death. The relationship between the overall competency of the host immune response and disease severity is not fully elucidated. 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.
Keywords: IL-17; LDHA; RORγt; mucosal-associated invariant T cells; sepsis