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Differential controls of MAIT cell effector polarization by mTORC1/mTORC2 via integrating cytokine and costimulatory signals.

Publication ,  Journal Article
Tao, H; Pan, Y; Chu, S; Li, L; Xie, J; Wang, P; Zhang, S; Reddy, S; Sleasman, JW; Zhong, X-P
Published in: Nat Commun
April 1, 2021

Mucosal-associated invariant T (MAIT) cells have important functions in immune responses against pathogens and in diseases, but mechanisms controlling MAIT cell development and effector lineage differentiation remain unclear. Here, we report that IL-2/IL-15 receptor β chain and inducible costimulatory (ICOS) not only serve as lineage-specific markers for IFN-γ-producing MAIT1 and IL-17A-producing MAIT17 cells, but are also important for their differentiation, respectively. Both IL-2 and IL-15 induce mTOR activation, T-bet upregulation, and subsequent MAIT cell, especially MAIT1 cell, expansion. By contrast, IL-1β induces more MAIT17 than MAIT1 cells, while IL-23 alone promotes MAIT17 cell proliferation and survival, but synergizes with IL-1β to induce strong MAIT17 cell expansion in an mTOR-dependent manner. Moreover, mTOR is dispensable for early MAIT cell development, yet pivotal for MAIT cell effector differentiation. Our results thus show that mTORC2 integrates signals from ICOS and IL-1βR/IL-23R to exert a crucial role for MAIT17 differentiation, while the IL-2/IL-15R-mTORC1-T-bet axis ensures MAIT1 differentiation.

Duke Scholars

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

April 1, 2021

Volume

12

Issue

1

Start / End Page

2029

Location

England

Related Subject Headings

  • TOR Serine-Threonine Kinases
  • Signal Transduction
  • Mucosal-Associated Invariant T Cells
  • Mice, Transgenic
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Mechanistic Target of Rapamycin Complex 2
  • Mechanistic Target of Rapamycin Complex 1
  • Lymphocyte Activation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Tao, H., Pan, Y., Chu, S., Li, L., Xie, J., Wang, P., … Zhong, X.-P. (2021). Differential controls of MAIT cell effector polarization by mTORC1/mTORC2 via integrating cytokine and costimulatory signals. Nat Commun, 12(1), 2029. https://doi.org/10.1038/s41467-021-22162-8
Tao, Huishan, Yun Pan, Shuai Chu, Lei Li, Jinhai Xie, Peng Wang, Shimeng Zhang, Srija Reddy, John W. Sleasman, and Xiao-Ping Zhong. “Differential controls of MAIT cell effector polarization by mTORC1/mTORC2 via integrating cytokine and costimulatory signals.Nat Commun 12, no. 1 (April 1, 2021): 2029. https://doi.org/10.1038/s41467-021-22162-8.
Tao H, Pan Y, Chu S, Li L, Xie J, Wang P, et al. Differential controls of MAIT cell effector polarization by mTORC1/mTORC2 via integrating cytokine and costimulatory signals. Nat Commun. 2021 Apr 1;12(1):2029.
Tao, Huishan, et al. “Differential controls of MAIT cell effector polarization by mTORC1/mTORC2 via integrating cytokine and costimulatory signals.Nat Commun, vol. 12, no. 1, Apr. 2021, p. 2029. Pubmed, doi:10.1038/s41467-021-22162-8.
Tao H, Pan Y, Chu S, Li L, Xie J, Wang P, Zhang S, Reddy S, Sleasman JW, Zhong X-P. Differential controls of MAIT cell effector polarization by mTORC1/mTORC2 via integrating cytokine and costimulatory signals. Nat Commun. 2021 Apr 1;12(1):2029.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

April 1, 2021

Volume

12

Issue

1

Start / End Page

2029

Location

England

Related Subject Headings

  • TOR Serine-Threonine Kinases
  • Signal Transduction
  • Mucosal-Associated Invariant T Cells
  • Mice, Transgenic
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Mechanistic Target of Rapamycin Complex 2
  • Mechanistic Target of Rapamycin Complex 1
  • Lymphocyte Activation