Tissue-restricted adaptive type 2 immunity is orchestrated by expression of the costimulatory molecule OX40L on group 2 innate lymphoid cells

Research output: Contribution to journalArticle

Authors

  • Timotheus Y F Halim
  • Batika M J Rana
  • Jennifer A Walker
  • Bernhard Kerscher
  • Martin D Knolle
  • Helen E Jolin
  • Eva M Serrao
  • Liora Haim-Vilmovsky
  • Sarah A Teichmann
  • Hans-Reimer Rodewald
  • Marina Botto
  • Timothy J Vyse
  • Padraic G Fallon
  • Andrew N J McKenzie

Colleges, School and Institutes

External organisations

  • University of Cambridge
  • MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
  • Mouse Pipelines, Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
  • Division of Cellular Immunology, German Cancer Research Center, Heidelberg 69120, Germany.
  • Imperial College London
  • King's College London
  • From the School of Biochemistry & Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
  • MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK. Electronic address: anm@mrc-lmb.cam.ac.uk.

Abstract

The local regulation of type 2 immunity relies on dialog between the epithelium and the innate and adaptive immune cells. Here we found that alarmin-induced expression of the co-stimulatory molecule OX40L on group 2 innate lymphoid cells (ILC2s) provided tissue-restricted T cell co-stimulation that was indispensable for Th2 and regulatory T (Treg) cell responses in the lung and adipose tissue. Interleukin (IL)-33 administration resulted in organ-specific surface expression of OX40L on ILC2s and the concomitant expansion of Th2 and Treg cells, which was abolished upon deletion of OX40L on ILC2s (Il7raCre/+Tnfsf4fl/fl mice). Moreover, Il7raCre/+Tnfsf4fl/fl mice failed to mount effective Th2 and Treg cell responses and corresponding adaptive type 2 pulmonary inflammation arising from Nippostrongylus brasiliensis infection or allergen exposure. Thus, the increased expression of OX40L in response to IL-33 acts as a licensing signal in the orchestration of tissue-specific adaptive type 2 immunity, without which this response fails to establish.

Details

Original languageEnglish
Pages (from-to)1195-1207.e6
Number of pages20
JournalImmunity
Volume48
Issue number6
Early online date12 Jun 2018
Publication statusPublished - 19 Jun 2018

Keywords

  • ILC2, OX40L, type 2 immunity, Th2 cells, Treg cells, allergy, helminth, IL-33