{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:02:14Z","timestamp":1790222534607,"version":"4.1.0"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T00:00:00Z","timestamp":1417392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Recent studies suggest a role for autophagy in the secretion of IL-1 cytokines regulating the development of inflammatory diseases. The antimalarial drug and autophagy\/lysosome inhibitor chloroquine (CHQ) is considered as potential trigger of drug-induced or drug-aggravated psoriasis, in which Th17 cells sustain a persistent inflammation. In this study, we investigated the effect of CHQ on human monocyte-derived Langerhans-like cells (MoLC) and dendritic cells (MoDC) in response to IL-1\u03b2. The presence of CHQ reduced IL-12p70 release in both subsets, but surprisingly increased IL-6 production in MoDC and IL-23 in MoLC. Importantly, CHQ-treated MoLC promoted IL-17A secretion by CD4+ T cells and elevated RORC mRNA levels, whereas IFN-\u03b3 release was reduced. The dysregulation of IL-12 family cytokines in MoLC and MoDC occurred at the transcriptional level. Similar effects were obtained with other late autophagy inhibitors, whereas PI3K inhibitor 3-methyladenine failed to increase IL-23 secretion. The modulated cytokine release was dependent on IL-1 cytokine activation and abrogated by a specific IL-1R antagonist. CHQ elevated expression of TNFR-associated factor 6, a common intermediate in IL-1R and TLR-dependent signaling. Accordingly, treatment with Pam3CSK4 and CHQ enhanced IL-23 release in MoLC and MoDC. CHQ inhibited autophagic flux, confirmed by increased LC3-II and p62 expression, and activated ERK, p38, and JNK MAPK, but only inhibition of p38 abrogated IL-23 release by MoLC. Thus, our findings indicate that CHQ modulates cytokine release in a p38-dependent manner, suggesting an essential role of Langerhans cells and dendritic cells in CHQ-provoked psoriasis, possibly by promoting Th17 immunity.<\/jats:p>","DOI":"10.4049\/jimmunol.1303276","type":"journal-article","created":{"date-parts":[[2014,11,11]],"date-time":"2014-11-11T05:02:31Z","timestamp":1415682151000},"page":"6135-6143","source":"Crossref","is-referenced-by-count":69,"title":["Chloroquine Promotes IL-17 Production by CD4+ T Cells via p38-Dependent IL-23 Release by Monocyte-Derived Langerhans-like Cells"],"prefix":"10.1093","volume":"193","author":[{"given":"Andr\u00e9","family":"Said","sequence":"first","affiliation":[{"name":"Pharmakologie und Toxikologie, Institut f\u00fcr Pharmazie, Freie Universit\u00e4t Berlin , D-14195 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Bock","sequence":"additional","affiliation":[{"name":"Pharmakologie und Toxikologie, Institut f\u00fcr Pharmazie, Freie Universit\u00e4t Berlin , D-14195 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trim","family":"Lajqi","sequence":"additional","affiliation":[{"name":"Pharmakologie und Toxikologie, Institut f\u00fcr Pharmazie, Freie Universit\u00e4t Berlin , D-14195 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerrit","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Pharmakologie und Toxikologie, Institut f\u00fcr Pharmazie, Freie Universit\u00e4t Berlin , D-14195 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4493-7597","authenticated-orcid":false,"given":"G\u00fcnther","family":"Weindl","sequence":"additional","affiliation":[{"name":"Pharmakologie und Toxikologie, Institut f\u00fcr Pharmazie, Freie Universit\u00e4t Berlin , D-14195 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,12,15]]},"reference":[{"key":"2025030707502214100_r1","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/nature07383","article-title":"Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production","volume":"456","author":"Saitoh","year":"2008","journal-title":"Nature"},{"key":"2025030707502214100_r2","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.chom.2009.05.016","article-title":"Autophagy, immunity, and microbial adaptations","volume":"5","author":"Deretic","year":"2009","journal-title":"Cell Host Microbe"},{"key":"2025030707502214100_r3","doi-asserted-by":"crossref","first-page":"ra42","DOI":"10.1126\/scisignal.2000751","article-title":"TRAF6 and A20 regulate lysine 63-linked ubiquitination of Beclin-1 to control TLR4-induced autophagy","volume":"3","author":"Shi","year":"2010","journal-title":"Sci. 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