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

Publication date: 19 June 2018
Source:Immunity, Volume 48, Issue 6
Author(s): 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
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.

Graphical abstract



Type 2 immunity underpins diverse processes central to tissue homeostasis, allergic inflammation, and anti-helminth immunity. Halim et al. demonstrate that the local expansion of Th2 and Treg cells in response to the alarmin IL-33 is dependent on the expression of the costimulatory molecule OX40L by type 2 innate lymphoid cells (ILC2s), revealing a central role for the IL-33-ILC2-OX40L pathway in the orchestration of type 2 immunity.