The adaptor protein CIKS/Act1 is essential for IL-25-mediated allergic airway inflammation.
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.
Claudio
Estefania
E
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Sønder
Søren Ulrik
SU
Saret
Sun
S
Carvalho
Gabrielle
G
Ramalingam
Thirumalai R
TR
Wynn
Thomas A
TA
Chariot
Alain
A
Garcia-Perganeda
Antonio
A
Leonardi
Antonio
A
Paun
Andrea
A
Chen
Amy
A
Ren
Nina Y
NY
Wang
Hongshan
H
Siebenlist
Ulrich
U
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D039521:CD11c Antigen / Q000096:biosynthesis; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000502:physiology*; D007378:Interleukins / Q000008:administration & dosage / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D018418:Th2 Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D039521:CD11c Antigen; D018836:Inflammation Mediators; D007378:Interleukins; C442281:Mydgf protein, mouse; C515963:Traf3ip2 protein, mouse