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CMTM4 is a subunit of the IL-17 receptor and mediates autoimmune pathology
D. Knizkova, M. Pribikova, H. Draberova, T. Semberova, T. Trivic, A. Synackova, A. Ujevic, J. Stefanovic, A. Drobek, M. Huranova, V. Niederlova, O. Tsyklauri, A. Neuwirth, J. Tureckova, O. Stepanek, P. Draber
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
NLK
ProQuest Central
od 2000-07-01 do Před 1 rokem
Health & Medicine (ProQuest)
od 2000-07-01 do Před 1 rokem
Public Health Database (ProQuest)
od 2000-07-01 do Před 1 rokem
- MeSH
- encefalomyelitida autoimunitní experimentální * genetika MeSH
- interleukin-17 metabolismus MeSH
- lidé MeSH
- myši MeSH
- proteiny obsahující MARVEL doménu genetika MeSH
- psoriatická artritida * MeSH
- psoriáza * MeSH
- receptory interleukinu-17 genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Interleukin-17A (IL-17A) is a key mediator of protective immunity to yeast and bacterial infections but also drives the pathogenesis of several autoimmune diseases, such as psoriasis or psoriatic arthritis. Here we show that the tetra-transmembrane protein CMTM4 is a subunit of the IL-17 receptor (IL-17R). CMTM4 constitutively associated with IL-17R subunit C to mediate its stability, glycosylation and plasma membrane localization. Both mouse and human cell lines deficient in CMTM4 were largely unresponsive to IL-17A, due to their inability to assemble the IL-17R signaling complex. Accordingly, CMTM4-deficient mice had a severe defect in the recruitment of immune cells following IL-17A administration and were largely resistant to experimental psoriasis, but not to experimental autoimmune encephalomyelitis. Collectively, our data identified CMTM4 as an essential component of IL-17R and a potential therapeutic target for treating IL-17-mediated autoimmune diseases.
Citace poskytuje Crossref.org
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- $a Knizkova, Daniela $u Laboratory of Immunity & Cell Communication, BIOCEV, First Faculty of Medicine, Charles University, Vestec, Czech Republic $u Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic
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- $a Interleukin-17A (IL-17A) is a key mediator of protective immunity to yeast and bacterial infections but also drives the pathogenesis of several autoimmune diseases, such as psoriasis or psoriatic arthritis. Here we show that the tetra-transmembrane protein CMTM4 is a subunit of the IL-17 receptor (IL-17R). CMTM4 constitutively associated with IL-17R subunit C to mediate its stability, glycosylation and plasma membrane localization. Both mouse and human cell lines deficient in CMTM4 were largely unresponsive to IL-17A, due to their inability to assemble the IL-17R signaling complex. Accordingly, CMTM4-deficient mice had a severe defect in the recruitment of immune cells following IL-17A administration and were largely resistant to experimental psoriasis, but not to experimental autoimmune encephalomyelitis. Collectively, our data identified CMTM4 as an essential component of IL-17R and a potential therapeutic target for treating IL-17-mediated autoimmune diseases.
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