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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
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
NLK
ProQuest Central
from 2000-07-01 to 1 year ago
Health & Medicine (ProQuest)
from 2000-07-01 to 1 year ago
Public Health Database (ProQuest)
from 2000-07-01 to 1 year ago
- MeSH
- Encephalomyelitis, Autoimmune, Experimental * genetics MeSH
- Interleukin-17 metabolism MeSH
- Humans MeSH
- Mice MeSH
- MARVEL Domain-Containing Proteins genetics MeSH
- Arthritis, Psoriatic * MeSH
- Psoriasis * MeSH
- Receptors, Interleukin-17 genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't 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.
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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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