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The Adaptor Protein CIKS/Act1 Is Essential for IL-25-Mediated Allergic Airway Inflammation

2009; American Association of Immunologists; Volume: 182; Issue: 3 Linguagem: Inglês

10.4049/jimmunol.182.3.1617

1550-6606

Estefanı́a Claudio, Søren Ulrik Sønder, Sun Saret, Gabrielle Carvalho, Thirumalai R. Ramalingam, Thomas A. Wynn, Alain Chariot, Antonio García‐Pergañeda, Antonio Leonardi, Andrea Paun, Amy Chen, Nina Ren, Hongshan Wang, Ulrich Siebenlist,

Pediatric health and respiratory diseases

Abstract IL-17 is the signature cytokine of recently discovered Th type 17 (Th17) cells, which are prominent in defense against extracellular bacteria and fungi as well as in autoimmune diseases, such as rheumatoid arthritis and experimental autoimmune encephalomyelitis in animal models. IL-25 is a member of the IL-17 family of cytokines, but has been associated with Th2 responses instead and may negatively cross-regulate Th17/IL-17 responses. IL-25 can initiate an allergic asthma-like inflammation in the airways, which includes recruitment of eosinophils, mucus hypersecretion, Th2 cytokine production, and airways hyperreactivity. We demonstrate that these effects of IL-25 are entirely dependent on the adaptor protein CIKS (also known as Act1). Surprisingly, this adaptor is necessary to transmit IL-17 signals as well, despite the very distinct biologic responses that these two cytokines elicit. We identify CD11c+ macrophage-like lung cells as physiologic relevant targets of IL-25 in vivo.