Differentiation of Type 17 Mucosal-Associated Invariant T Cells in Circulation Contributes to the Severity of Sepsis

This study identified a higher proportion of circulating MAIT17 with expression of IL-17A and RAR-related orphan receptor γt in patients with sepsis. The proportion of MAIT17 was correlated with the severity of sepsis. Single-cell RNA-sequencing analysis revealed an enhanced expression of lactate dehydrogenase A (LDHA) in MAIT17 in patients with sepsis. Cell-culture experiments demonstrated that phosphoinositide 3-kinase-LDHA signaling was required for RAR-related orphan receptor γt expression in MAIT17. Finally, the elevated levels of plasma IL-18 promoted the differentiation of circulating MAIT17 cells in sepsis. In summary, this study reveals a new role of circulating MAIT17 in promoting sepsis severity and suggests the phosphoinositide 3-kinase-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