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Area of Science:

  • Immunology
  • Evolutionary Biology
  • Comparative Genomics

Background:

  • T cells are crucial for adaptive immunity, first appearing in jawed fish approximately 450 million years ago.
  • Studying fish T cells offers insights into the evolution of adaptive immune systems.
  • The mechanistic target of rapamycin complex 1 (mTORC1) pathway is a key regulator in mammalian immunity.

Purpose of the Study:

  • To elucidate the regulatory mechanisms of adaptive immunity mediated by ancestral T cells in jawed fish.
  • To investigate the role of the mTORC1 pathway in Nile tilapia T cell responses during bacterial infection.
  • To understand the evolutionary conservation of T cell regulatory strategies.

Main Methods:

  • Utilized a Nile tilapia (Oreochromis niloticus) model to study T cell adaptive immunity.
  • Investigated the effects of rapamycin, an mTORC1 inhibitor, on T cell activation and proliferation during Streptococcus agalactiae infection.
  • Analyzed the molecular mechanisms linking mTORC1 signaling to metabolic reprogramming and effector functions in T cells.

Main Results:

  • Nile tilapia T cells and the mTORC1 pathway are involved in adaptive immune responses to S. agalactiae.
  • mTORC1 inhibition by rapamycin impairs T cell activation and proliferation in Nile tilapia.
  • mTORC1 signaling is essential for primordial effector T cells to clear infection by promoting inflammatory, cytotoxic, and proapoptotic gene expression via metabolic reprogramming.

Conclusions:

  • Teleost mTORC1 coordinates metabolic programs (glycolysis, glutaminolysis, lipogenesis) through transcription factors (c-Myc, HIF-1α, SREBPs), linking immune signals to metabolic adaptation in jawed fish.
  • This study provides the first description of T cell-mediated adaptive immunity regulation in a fish species.
  • Primordial T cells in jawed fish possess sophisticated regulatory mechanisms similar to modern T cells, predating the divergence of bony fish and tetrapods.