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Cross-talk between ILC2 and Gata3high Tregs locally constrains adaptive type 2 immunity.
Stockis, Julie; Yip, Thomas; Moreno-Vicente, Julia; Burton, Oliver; Samarakoon, Youhani; Schuijs, Martijn J; Raghunathan, Shwetha; Garcia, Celine; Luo, Weike; Whiteside, Sarah K; Png, Shaun; Simpson, Charlotte; Monk, Stela; Sawle, Ashley; Yin, Kelvin; Barbieri, Johanna; Papadopoulos, Panagiotis; Wong, Hannah; Rodewald, Hans-Reimer; Vyse, Timothy; McKenzie, Andrew N J; Cragg, Mark S; Hoare, Matthew; Withers, David R; Fehling, Hans Jörg; Roychoudhuri, Rahul; Liston, Adrian; Halim, Timotheus Y F.
Afiliación
  • Stockis J; CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Yip T; CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Moreno-Vicente J; CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Burton O; Immunology Programme, Babraham Institute, Cambridge CB22 3AT, UK.
  • Samarakoon Y; Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
  • Schuijs MJ; CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Raghunathan S; CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Garcia C; CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Luo W; CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Whiteside SK; CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Png S; Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
  • Simpson C; CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Monk S; CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Sawle A; CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Yin K; CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Barbieri J; CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Papadopoulos P; CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Wong H; CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Rodewald HR; Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
  • Vyse T; Division of Cellular Immunology, German Cancer Research Center, Heidelberg 69120, Germany.
  • McKenzie ANJ; Department of Medical and Molecular Genetics, King's College London, London SE1 9RT, UK.
  • Cragg MS; Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
  • Hoare M; Antibody and Vaccine Group, Centre for Cancer Immunology, School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
  • Withers DR; CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.
  • Fehling HJ; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
  • Roychoudhuri R; Early Cancer Institute, Hutchison Research Centre, University of Cambridge, Cambridge CB2 0XZ, UK.
  • Liston A; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.
  • Halim TYF; Institute of Immunology, University Hospital Ulm, Ulm 89081, Germany.
Sci Immunol ; 9(97): eadl1903, 2024 Jul 19.
Article en En | MEDLINE | ID: mdl-39028828
ABSTRACT
Regulatory T cells (Tregs) control adaptive immunity and restrain type 2 inflammation in allergic disease. Interleukin-33 promotes the expansion of tissue-resident Tregs and group 2 innate lymphoid cells (ILC2s); however, how Tregs locally coordinate their function within the inflammatory niche is not understood. Here, we show that ILC2s are critical orchestrators of Treg function. Using spatial, cellular, and molecular profiling of the type 2 inflamed niche, we found that ILC2s and Tregs engage in a direct (OX40L-OX40) and chemotaxis-dependent (CCL1-CCR8) cellular dialogue that enforces the local accumulation of Gata3high Tregs, which are transcriptionally and functionally adapted to the type 2 environment. Genetic interruption of ILC2-Treg communication resulted in uncontrolled type 2 lung inflammation after allergen exposure. Mechanistically, we found that Gata3high Tregs can modulate the local bioavailability of the costimulatory molecule OX40L, which subsequently controlled effector memory T helper 2 cell numbers. Hence, ILC2-Treg interactions represent a critical feedback mechanism to control adaptive type 2 immunity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T Reguladores / Factor de Transcripción GATA3 / Inmunidad Adaptativa / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Sci Immunol Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T Reguladores / Factor de Transcripción GATA3 / Inmunidad Adaptativa / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Sci Immunol Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido