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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.<\/jats:p>","DOI":"10.1038\/s41590-022-01325-9","type":"journal-article","created":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T16:19:16Z","timestamp":1666369156000},"page":"1644-1652","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["CMTM4 is a subunit of the IL-17 receptor and mediates autoimmune pathology"],"prefix":"10.1038","volume":"23","author":[{"given":"Daniela","family":"Knizkova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5105-9609","authenticated-orcid":false,"given":"Michaela","family":"Pribikova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Draberova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6756-2137","authenticated-orcid":false,"given":"Tereza","family":"Semberova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2566-253X","authenticated-orcid":false,"given":"Tijana","family":"Trivic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6854-4405","authenticated-orcid":false,"given":"Alzbeta","family":"Synackova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2176-5585","authenticated-orcid":false,"given":"Andrea","family":"Ujevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4164-2726","authenticated-orcid":false,"given":"Jana","family":"Stefanovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ales","family":"Drobek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Huranova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8768-9039","authenticated-orcid":false,"given":"Veronika","family":"Niederlova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9997-5913","authenticated-orcid":false,"given":"Oksana","family":"Tsyklauri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4668-4316","authenticated-orcid":false,"given":"Ales","family":"Neuwirth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolana","family":"Tureckova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2735-3311","authenticated-orcid":false,"given":"Ondrej","family":"Stepanek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8658-4614","authenticated-orcid":false,"given":"Peter","family":"Draber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,21]]},"reference":[{"key":"1325_CR1","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1038\/nri2800","volume":"10","author":"DJ Cua","year":"2010","unstructured":"Cua, D. 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