The adaptor protein CIKS/Act1 is essential for IL-25-mediated allergic airway inflammation1

IL-17 is the signature cytokine of recently discovered T helper 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 mem...

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Bibliographic Details
Published in:	The Journal of immunology (1950) Vol. 182; no. 3; pp. 1617 - 1630
Main Authors:	Claudio, Estefania, Sønder, Søren Ulrik, Saret, Sun, Carvalho, Gabrielle, Ramalingam, Thirumalai R, Wynn, Thomas A, Chariot, Alain, Garcia-Perganeda, Antonio, Leonardi, Antonio, Paun, Andrea, Chen, Amy, Ren, Nina Y., Wang, Hongshan, Siebenlist, Ulrich
Format:	Journal Article
Language:	English
Published:	01-02-2009
Online Access:	Get full text
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Summary:	IL-17 is the signature cytokine of recently discovered T helper 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 (a.k.a. Act1). Surprisingly, this adaptor is necessary to transmit IL-17 signals as well, despite the very distinct biologic responses these two cytokines elicit. We identify CD11c + macrophage-like lung cells as physiologic relevant targets of IL-25 in vivo .
Bibliography:	Current address: Department of Medical Biochemistry and Molecular Biology, The University of Seville School of Medicine, Avda. Sánchez Pizjuan 4, 41009 Seville, Spain Current address: Institut National de la Santé et de la Recherche Médicale, Unité 542, Université Paris-Sud, Hôpital Paul Brousse, Villejuif, France. Current address: Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), GIGA Signal Transduction, Unit of Medical Chemistry,University of Liege, Sart-Tilman, 4000 Liège, Belgium Current address: Dipartimento di Biologia e Patologia Cellulare e Molecolare, “Federico II” University of Naples, Via Pansini 5, Naples 80131, Italy Address correspondence and reprint requests to Dr. Ulrich Siebenlist, NIH, Bldg. 10, Rm. 11B15, Bethesda, MD, 20892-1876. E-mail address: USiebenlist@niaid.nih.gov
ISSN:	0022-1767 1550-6606