Tissue-Restricted Adaptive Type 2 Immunity Is Orchestrated by Expression of the Costimulatory Molecule OX40L on Group 2 Innate Lymphoid Cells

Immunity. 2018 Jun 19;48(6):1195-1207.e6. doi: 10.1016/j.immuni.2018.05.003. Epub 2018 Jun 12.


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.

Keywords: IL-33; ILC2; OX40L; Th2 cells; Treg cells; allergy; helminth; type 2 immunity.

MeSH terms

  • Adaptive Immunity / immunology*
  • Animals
  • Cell Differentiation / immunology
  • Immunity, Innate / immunology*
  • Interleukin-33 / immunology
  • Lymphocyte Activation / immunology
  • Lymphocytes / immunology
  • Membrane Glycoproteins / immunology*
  • Mice
  • OX40 Ligand
  • T-Lymphocytes, Regulatory / immunology*
  • Th2 Cells / immunology*
  • Tumor Necrosis Factors / immunology*


  • Il33 protein, mouse
  • Interleukin-33
  • Membrane Glycoproteins
  • OX40 Ligand
  • Tnfsf4 protein, mouse
  • Tumor Necrosis Factors