Repository logo
 

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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Halim, Timotheus YF 
Rana, Batika MJ 
Walker, Jennifer A 
Kerscher, Bernhard 
Knolle, Martin D 

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.

Description

Keywords

IL-33, ILC2, OX40L, Th2 cells, Treg cells, allergy, helminth, type 2 immunity, Adaptive Immunity, Animals, Cell Differentiation, Immunity, Innate, Interleukin-33, Lymphocyte Activation, Lymphocytes, Membrane Glycoproteins, Mice, OX40 Ligand, T-Lymphocytes, Regulatory, Th2 Cells, Tumor Necrosis Factors

Journal Title

Immunity

Conference Name

Journal ISSN

1074-7613
1097-4180

Volume Title

48

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (204622/Z/16/Z)
Cancer Research UK (24995)
ERC, EMBL