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Although activation of the AP\u20101 transcription factor complex is common in TLR signaling, the specific involvement and induced targets remain poorly understood. Here, we investigated the role of c\u2010Jun\/AP\u20101 protein in skin inflammation following TLR7 activation using human psoriatic skin, dendritic cells (DC), and genetically engineered mouse models. We show that c\u2010Jun regulates CCL2 production in DCs leading to impaired recruitment of plasmacytoid DCs to inflamed skin after treatment with the TLR7\/8 agonist Imiquimod. Furthermore, deletion of c\u2010Jun in DCs or chemical blockade of JNK\/c\u2010Jun signaling ameliorates psoriasis\u2010like skin inflammation by reducing IL\u201023 production in DCs. Importantly, the control of IL\u201023 and CCL2 by c\u2010Jun is most pronounced in murine type\u20102 DCs. CCL2 and IL\u201023 expression co\u2010localize with c\u2010Jun in type\u20102\/inflammatory DCs in human psoriatic skin and JNK\u2010AP\u20101 inhibition reduces the expression of these targets in TLR7\/8\u2010stimulated human DCs. Therefore, c\u2010Jun\/AP\u20101 is a central driver of TLR7\u2010induced immune responses by DCs and JNK\/c\u2010Jun a potential therapeutic target in psoriasis.<\/jats:p>","DOI":"10.15252\/emmm.202012409","type":"journal-article","created":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T17:06:25Z","timestamp":1615914385000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Psoriatic skin inflammation is promoted by c\u2010Jun\/AP\u20101\u2010dependent CCL2 and IL\u201023 expression in dendritic cells"],"prefix":"10.1038","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1398-9140","authenticated-orcid":false,"given":"Philipp","family":"Novoszel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Holcmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Stulnig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiano","family":"De Sa Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Zyulina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabela","family":"Borek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Linder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Bogusch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1155-2869","authenticated-orcid":false,"given":"Barbara","family":"Drobits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3123-6342","authenticated-orcid":false,"given":"Carmen","family":"Tam\u2010Amersdorfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick M","family":"Brunner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Stary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Latifa","family":"Bakiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7872-0196","authenticated-orcid":false,"given":"Erwin F","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert","family":"Strobl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6129-5613","authenticated-orcid":false,"given":"Maria","family":"Sibilia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,16]]},"reference":[{"key":"BFEMMM202012409_CR1","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.cyto.2017.12.010","volume":"110","author":"S Behfar","year":"2018","unstructured":"Behfar S, Hassanshahi G, Nazari A, Khorramdelazad H (2018) A brief look at the role of monocyte chemoattractant protein\u20101 (CCL2) in the pathophysiology of psoriasis. 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