Cross-talk between ILC2 and Gata3 <sup>high</sup> T <sub>regs</sub> locally constrains adaptive type 2 immunity-Reference-Cited by-同舟云学术

Cross-talk between ILC2 and Gata3 ^high T _regs locally constrains adaptive type 2 immunity

Published:2024-07-19 Issue:97 Volume:9 Page:
ISSN:2470-9468
Container-title:Science Immunology
language:en
Short-container-title:Sci. Immunol.

Author:

Stockis Julie¹^ORCID,Yip Thomas¹^ORCID,Moreno-Vicente Julia¹^ORCID,Burton Oliver²³^ORCID,Samarakoon Youhani¹,Schuijs Martijn J.¹^ORCID,Raghunathan Shwetha¹,Garcia Celine¹,Luo Weike¹^ORCID,Whiteside Sarah K.³^ORCID,Png Shaun¹^ORCID,Simpson Charlotte¹,Monk Stela¹^ORCID,Sawle Ashley¹^ORCID,Yin Kelvin¹^ORCID,Barbieri Johanna¹^ORCID,Papadopoulos Panagiotis¹^ORCID,Wong Hannah⁴^ORCID,Rodewald Hans-Reimer⁵,Vyse Timothy⁶^ORCID,McKenzie Andrew N. J.⁷^ORCID,Cragg Mark S.⁸^ORCID,Hoare Matthew¹⁹¹⁰^ORCID,Withers David R.¹¹^ORCID,Fehling Hans Jörg¹²^ORCID,Roychoudhuri Rahul³^ORCID,Liston Adrian²³^ORCID,Halim Timotheus Y. F.¹^ORCID

Affiliation:

1. CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.

2. Immunology Programme, Babraham Institute, Cambridge CB22 3AT, UK.

3. Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.

4. Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.

5. Division of Cellular Immunology, German Cancer Research Center, Heidelberg 69120, Germany.

6. Department of Medical and Molecular Genetics, King’s College London, London SE1 9RT, UK.

7. Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.

8. Antibody and Vaccine Group, Centre for Cancer Immunology, School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.

9. Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.

10. Early Cancer Institute, Hutchison Research Centre, University of Cambridge, Cambridge CB2 0XZ, UK.

11. Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.

12. Institute of Immunology, University Hospital Ulm, Ulm 89081, Germany.

Abstract

Regulatory T cells (T regs ) control adaptive immunity and restrain type 2 inflammation in allergic disease. Interleukin-33 promotes the expansion of tissue-resident T regs and group 2 innate lymphoid cells (ILC2s); however, how T regs locally coordinate their function within the inflammatory niche is not understood. Here, we show that ILC2s are critical orchestrators of T reg function. Using spatial, cellular, and molecular profiling of the type 2 inflamed niche, we found that ILC2s and T regs engage in a direct (OX40L-OX40) and chemotaxis-dependent (CCL1-CCR8) cellular dialogue that enforces the local accumulation of Gata3 high T regs , which are transcriptionally and functionally adapted to the type 2 environment. Genetic interruption of ILC2-T reg communication resulted in uncontrolled type 2 lung inflammation after allergen exposure. Mechanistically, we found that Gata3 high T regs can modulate the local bioavailability of the costimulatory molecule OX40L, which subsequently controlled effector memory T helper 2 cell numbers. Hence, ILC2-T reg interactions represent a critical feedback mechanism to control adaptive type 2 immunity.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciimmunol.adl1903

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