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 journal › Article
Colleges, School and Institutes
- 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: firstname.lastname@example.org.
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.
|Number of pages||20|
|Early online date||12 Jun 2018|
|Publication status||Published - 19 Jun 2018|
- ILC2, OX40L, type 2 immunity, Th2 cells, Treg cells, allergy, helminth, IL-33