Authors: Han, Yingying; Mora, Javier; Huard, Arnaud; da Silva, Priscila; Wiechmann, Svenja; Putyrski, Mateusz; Schuster, Christian; Elwakeel, Eiman; Lang, Guangping; Scholz, Anica; Scholz, Tatjana; Schmid, Tobias; de Bruin, Natasja; Billuart, Pierre; Sala, Carlo; Burkhardt, Harald; Parnham, Michael J.; Ernst, Andreas; Brüne, Bernhard; Weigert, Andreas
Online: https://linkinghub.elsevier.com/retrieve/pii/S2211-1247(19)30421-8
Issue: Cell Rep. 2019 Apr 16;27(3):835-846.e5.
Abstract
Interleukin-38 (IL-38) is a cytokine of the IL-1 family with a role in chronic inflammation. However, its main cellular targets and receptors remain obscure. IL-38 is highly expressed in the skin and downregulated in psoriasis patients. We report an investigation in cellular targets of IL-38 during the progression of imiquimod-induced psoriasis. In this model, IL-38 knockout (IL-38 KO) mice show delayed disease resolution with exacerbated IL-17-mediated inflammation, which is reversed by the administration of mature IL-38 or γδ T cell-receptor-blocking antibodies. Mechanistically, X-linked IL-1 receptor accessory protein-like 1 (IL1RAPL1) is upregulated upon γδ T cell activation to feedforward-amplify IL-17 production and is required for IL-38 to suppress γδ T cell IL-17 production. Accordingly, psoriatic IL1RAPL1 KO mice show reduced inflammation and IL-17 production by γδ T cells. Our findings indicate a role for IL-38 in the regulation of γδ T cell activation through IL1RAPL1, with consequences for auto-inflammatory disease.
