{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T05:47:34Z","timestamp":1769233654387,"version":"3.49.0"},"reference-count":55,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"808","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Signal."],"published-print":{"date-parts":[[2023,10,24]]},"abstract":"<jats:p>\n            The cytokine interleukin-17 (IL-17) is secreted by T helper 17 (T\n            <jats:sub>H<\/jats:sub>\n            17) cells and is beneficial for microbial control; however, it also causes inflammation and pathological tissue remodeling in autoimmunity. Hence, T\n            <jats:sub>H<\/jats:sub>\n            17 cell differentiation and IL-17 production must be tightly regulated, but, to date, this has been defined only in terms of transcriptional control. Phosphatidylinositols are second messengers produced during T cell activation that transduce signals from the T cell receptor (TCR) and costimulatory receptors at the plasma membrane. Here, we found that phosphatidylinositol 4,5-bisphosphate (PIP\n            <jats:sub>2<\/jats:sub>\n            ) was enriched in the nuclei of human T\n            <jats:sub>H<\/jats:sub>\n            17 cells, which depended on the kinase PIP5K1\u03b1, and that inhibition of PIP5K1\u03b1 impaired IL-17A production. In contrast, nuclear PIP\n            <jats:sub>2<\/jats:sub>\n            enrichment was not observed in T\n            <jats:sub>H<\/jats:sub>\n            1 or T\n            <jats:sub>H<\/jats:sub>\n            2 cells, and these cells did not require PIP5K1\u03b1 for cytokine production. In T cells from people with multiple sclerosis, IL-17 production elicited by myelin basic protein was blocked by PIP5K1\u03b1 inhibition. IL-17 protein was affected without altering either the abundance or stability of\n            <jats:italic>IL17A<\/jats:italic>\n            mRNA in T\n            <jats:sub>H<\/jats:sub>\n            17 cells. Instead, analysis of PIP5K1\u03b1-associating proteins revealed that PIP5K1\u03b1 interacted with ARS2, a nuclear cap-binding complex scaffold protein, to facilitate its binding to\n            <jats:italic>IL17A<\/jats:italic>\n            mRNA and subsequent IL-17A protein production. These findings highlight a transcription-independent, translation-dependent mechanism for regulating IL-17A protein production that might be relevant to other cytokines.\n          <\/jats:p>","DOI":"10.1126\/scisignal.abo6555","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T17:58:50Z","timestamp":1698170330000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Human IL-17A protein production is controlled through a PIP5K1\u03b1-dependent translational checkpoint"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0323-7628","authenticated-orcid":true,"given":"Shankar K.","family":"Revu","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0607-1058","authenticated-orcid":true,"given":"Wenjuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14850, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhivyaa","family":"Rajasundaram","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA 15261, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4177-5203","authenticated-orcid":true,"given":"Alexander","family":"Brady","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14850, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6591-9515","authenticated-orcid":true,"given":"Saikat","family":"Majumder","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8511-2041","authenticated-orcid":true,"given":"Sarah L.","family":"Gaffen","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8371-3345","authenticated-orcid":true,"given":"William","family":"Hawse","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1500-2589","authenticated-orcid":true,"given":"Zongqi","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15261 USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5029-1668","authenticated-orcid":true,"given":"Mandy J.","family":"McGeachy","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA."},{"name":"Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14850, 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