[en] 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.
Research Center/Unit :
Giga-Signal Transduction - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Claudio, Estefania; National Institutes of Health > Laboratory of Immunoregulation
Sonder, Soren Ulrik; National Institutes of Health > Laboratory of Immunoregulation
Saret, Sun; National Institutes of Health > Laboratory of Immunoregulation
Carvalho, Gabrielle; National Institutes of Health > Laboratory of Immunoregulation
Ramalingam, Thirumalai R.; National Institutes of Health > Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases
Wynn, Thomas A.; National Institutes of Health > Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases
Chariot, Alain ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Garcia-Perganeda, Antonio; National Institutes of Health > Laboratory of Immunoregulation
Leonardi, Antonio; National Institutes of Health > Laboratory of Immunoregulation
Paun, Andrea; National Institutes of Health > Laboratory of Immunoregulation
Chen, Amy; National Institutes of Health > National Human Genome Research Institute
Ren, Nina Y.; National Institutes of Health > Laboratory of Immunoregulation
Wang, Hongshan; National Institutes of Health > Laboratory of Immunoregulation
Siebenlist, Ulrich; National Institutes of Health > Laboratory of Immunoregulation
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