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

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, Zhi Li, David R Withers, Andrew N J McKenzie

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94 Citations (Scopus)
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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.

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

Keywords

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

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