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Transcriptomes and metabolism define mouse and human MAIT cell populations.

Shilpi Chandra1,2, Gabriel Ascui1,2,3, Thomas Riffelmacher1,2,4

  • 1Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.

Science Immunology
|November 10, 2023
PubMed
Summary

Mucosal-associated invariant T (MAIT) cells exhibit distinct metabolic profiles, with MAIT17 cells showing increased lipid metabolism. Environmental factors can influence MAIT cell populations, impacting their function.

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Area of Science:

  • Immunology
  • Cell Biology
  • Metabolomics

Background:

  • Mucosal-associated invariant T (MAIT) cells are critical immune cells responding to microbial metabolites.
  • Understanding MAIT cell heterogeneity and development is key to deciphering their role in immunity.

Purpose of the Study:

  • To characterize MAIT cell populations across different organs.
  • To elucidate the developmental pathways and metabolic states of mouse and human MAIT cells in the thymus and periphery.

Main Methods:

  • Single-cell RNA sequencing
  • Phenotypic analysis
  • Metabolic assays
  • Comparative analysis of mouse and human MAIT cells

Main Results:

  • Mouse MAIT17 cells display distinct transcriptomes and metabolic states, including increased lipid uptake and mitochondrial potential, compared to MAIT1 cells.
  • Human MAIT cells show tissue-specific differences and increased lipid metabolism, similar to CD8 T resident memory cells, but lack elevated mitochondrial potential.
  • MAIT cell transcriptomes diverge significantly between mouse and human in the periphery, despite thymic similarities.
  • Environmental factors, such as housing conditions in pet store mice, impact lung MAIT17 cell populations.

Conclusions:

  • MAIT cell subsets possess unique metabolic identities, likely established during thymic development and maintained in peripheral tissues.
  • Environmental influences significantly shape MAIT cell subsets and their functions.
  • Further research into MAIT cell metabolism and environmental interactions is warranted for immune health.