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Differential controls of MAIT cell effector polarization by mTORC1/mTORC2 via integrating cytokine and costimulatory signals.
Tao, Huishan; Pan, Yun; Chu, Shuai; Li, Lei; Xie, Jinhai; Wang, Peng; Zhang, Shimeng; Reddy, Srija; Sleasman, John W; Zhong, Xiao-Ping.
Afiliación
  • Tao H; Department of Pediatrics-Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.
  • Pan Y; Department of Pediatrics-Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.
  • Chu S; Department of Pediatrics-Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.
  • Li L; Department of Pediatrics-Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.
  • Xie J; Department of Pediatrics-Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.
  • Wang P; Department of Pediatrics-Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.
  • Zhang S; Department of Pediatrics-Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.
  • Reddy S; Department of Pediatrics-Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.
  • Sleasman JW; Department of Pediatrics-Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.
  • Zhong XP; Department of Pediatrics-Allergy and Immunology, Duke University Medical Center, Durham, NC, USA. xiaoping.zhong@duke.edu.
Nat Commun ; 12(1): 2029, 2021 04 01.
Article en En | MEDLINE | ID: mdl-33795689
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 ß 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-1ß induces more MAIT17 than MAIT1 cells, while IL-23 alone promotes MAIT17 cell proliferation and survival, but synergizes with IL-1ß 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-1ßR/IL-23R to exert a crucial role for MAIT17 differentiation, while the IL-2/IL-15R-mTORC1-T-bet axis ensures MAIT1 differentiation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Activación de Linfocitos / Citocinas / Proteína Coestimuladora de Linfocitos T Inducibles / Células T Invariantes Asociadas a Mucosa / Diana Mecanicista del Complejo 1 de la Rapamicina / Diana Mecanicista del Complejo 2 de la Rapamicina Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Activación de Linfocitos / Citocinas / Proteína Coestimuladora de Linfocitos T Inducibles / Células T Invariantes Asociadas a Mucosa / Diana Mecanicista del Complejo 1 de la Rapamicina / Diana Mecanicista del Complejo 2 de la Rapamicina Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido