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

2018; Cell Press; Volume: 48; Issue: 6 Linguagem: Inglês

10.1016/j.immuni.2018.05.003

1097-4180

Timotheus Y.F. Halim, Batika M.J. Rana, Jennifer A. Walker, Bernhard Kerscher, Martin 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,

Eosinophilic Esophagitis

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.