| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Laboratory of Immunoregulation and
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, and
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Intramural Research Program of National Institute of Allergy and Infectious Diseases, National Institutes of Health.
2 Current address: Institut National de la Santé et de la Recherche Médicale, Unité 542, Université Paris-Sud, Hôpital Paul Brousse, Villejuif, France.
3 Current address: Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), GIGA Signal Transduction, Unit of Medical Chemistry, University of Liege, Sart-Tilman, 4000 Liège, Belgium.
4 Current address: Department of Medical Biochemistry and Molecular Biology, University of Seville School of Medicine, Avda. Sánchez Pizjuan 4, 41009 Seville, Spain.
5 Current address: Dipartimento di Biologia e Patologia Cellulare e Molecolare, "Federico II" University of Naples, Via Pansini 5, Naples 80131, Italy.
6 Address correspondence and reprint requests to Dr. Ulrich Siebenlist, National Institutes of Health, Building 10, Room 11B15, Bethesda, MD 20892-1876. E-mail address: USiebenlist{at}niaid.nih.gov
7 Abbreviations used in this paper: AHR, airways hyperreactivity; BAFF, B cell-activating factor belonging to the TNF family; BALF, bronchoalveolar lavage fluid; BMDC, bone marrow-derived dendritic cell; BMDM, bone marrow-derived macrophage; Ct, cycle threshold; HA, hemagglutinin; HPRT, hypoxanthine phosphoribosyltransferase; i.n., intranasal; int, intermediate; KO, knockout; MEF, mouse embryo fibroblast; NP-KLH, 4-hydroxy-3-nitrophenylacetyl hapten-keyhole limpet hemocyanin; PAS, periodic acid-Schiff; SSC, side scatter; WT, wild type; CIKS, connection to I
B kinase and stress-activated protein kinase; SEFIR, similar expression to fibroblast growth factor genes and IL-17Rs.
8 The online version of this article contains supplementary material.
Related articles in The JI:
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
