The Adaptor Protein CIKS/Act1 is Essential for IL-25-mediated Allergic Airway Inflammation

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2009 Jan 22

PMID 19155511

Citations 82

Authors

Estefania Claudio

Soren Ulrik Sonder

Sun Saret

Gabrielle Carvalho

Thirumalai R Ramalingam

Thomas A Wynn

Alain Chariot

Antonio Garcia-Perganeda

Antonio Leonardi

Andrea Paun

Amy Chen

Nina Y Ren

Hongshan Wang

Ulrich Siebenlist

Affiliations

Soon will be listed here.

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.

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