2. Academic Validation
  3. Differentiation of Type 17 Mucosal-Associated Invariant T Cells in Circulation Contributes to the Severity of Sepsis

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

  • Am J Pathol. 2024 Jul;194(7):1248-1261. doi: 10.1016/j.ajpath.2024.03.010.
Xinying Li 1,  Sicheng Fu 2,  Hao Cheng 3,  Min Ma 4,  Zijian Song 5,  Jun Li 6,  Shuang Wu 5,  Chong Zhang 7,  Xiaoxia Wang 8,  Maoyu Tang 9,  Xuexue Pu 6,  Qiang Ji 6,  Jinquan Liang 6,  Zhibin Zhao 4,  Heinrich Körner 10,  Bin Li 11,  Min Shao 12,  Hua Wang 13
Affiliations

Affiliations

  • 1 Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China; School of Life Sciences, Anhui Medical University, Hefei, China.
  • 2 School of Basic Medical Sciences, University of Science and Technology of China, Hefei, China.
  • 3 Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen, China.
  • 4 Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
  • 5 School of Pharmacy, Anhui Medical University, Hefei, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, China.
  • 6 Department of Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
  • 7 Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
  • 8 School of Public Health, Anhui Medical University, Hefei, China.
  • 9 School of Basic Medical Sciences, Anhui Medical University, Hefei, China; Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, China.
  • 10 Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
  • 11 Center for Immune-Related Diseases at Shanghai Institute of Immunology, Departments of Respiratory and Critical Care Medicine and Thoracic Surgery, Ruijin Hospital, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 12 Department of Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: shaomin@ahmu.edu.cn.
  • 13 Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, China. Electronic address: wanghua@ahmu.edu.cn.
PMID: 38599461 DOI: 10.1016/j.ajpath.2024.03.010
Abstract

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 retinoic acid receptor-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 retinoic acid receptor-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.

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