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  2. Glutamine Metabolism Underlies the Functional Similarity of T Cells between Nile Tilapia and Tetrapod

Glutamine Metabolism Underlies the Functional Similarity of T Cells between Nile Tilapia and Tetrapod

  • Adv Sci (Weinh). 2023 Mar 8;e2201164. doi: 10.1002/advs.202201164.
Kang Li 1 2 Xiumei Wei 1 2 Xinying Jiao 1 2 Wenhai Deng 3 Jiaqi Li 1 2 Wei Liang 1 2 Yu Zhang 1 Jialong Yang 1 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
  • 2 Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China.
  • 3 School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Abstract

As the lowest organisms possessing T cells, fish are instrumental for understanding T cell evolution and immune defense in early vertebrates. This study established in Nile tilapia models suggests that T cells play a critical role in resisting Edwardsiella piscicida Infection via cytotoxicity and are essential for IgM+ B cell response. CD3 and CD28 monoclonal antibody crosslinking reveals that full activation of tilapia T cells requires the first and secondary signals, while Ca2+ -NFAT, MAPK/ERK, NF-κB, and mTORC1 pathways and IgM+ B cells collectively regulate T cell activation. Thus, despite the large evolutionary distance, tilapia and mammals such as mice and humans exhibit similar T cell functions. Furthermore, it is speculated that transcriptional networks and metabolic reprogramming, especially c-Myc-mediated glutamine metabolism triggered by mTORC1 and MAPK/ERK pathways, underlie the functional similarity of T cells between tilapia and mammals. Notably, tilapia, frogs, chickens, and mice utilize the same mechanisms to facilitate glutaminolysis-regulated T cell responses, and restoration of the glutaminolysis pathway using tilapia components rescues the immunodeficiency of human Jurkat T cells. Thus, this study provides a comprehensive picture of T cell immunity in tilapia, sheds novel perspectives for understanding T cell evolution, and offers potential avenues for intervening in human immunodeficiency.

Keywords

T cells; evolution; functional similarity; glutamine metabolism; tilapia.

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