{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T18:10:35Z","timestamp":1789668635744,"version":"4.0.1"},"reference-count":108,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T00:00:00Z","timestamp":1701216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["RD\/0119-DST0000-10"],"award-info":[{"award-number":["RD\/0119-DST0000-10"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["RD\/0119-ICMR000-001"],"award-info":[{"award-number":["RD\/0119-ICMR000-001"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Immune cell\u2013derived IL-17A is one of the key pathogenic cytokines in psoriasis, an immunometabolic disorder. Although IL-17A is an established regulator of cutaneous immune cell biology, its functional and metabolic effects on nonimmune cells of the skin, particularly keratinocytes, have not been comprehensively explored. Using multiomics profiling and systems biology\u2013based approaches, we systematically uncover significant roles for IL-17A in the metabolic reprogramming of human primary keratinocytes (HPKs). High-throughput liquid chromatography\u2013tandem mass spectrometry and nuclear magnetic resonance spectroscopy revealed IL-17A\u2013dependent regulation of multiple HPK proteins and metabolites of carbohydrate and lipid metabolism. Systems-level MitoCore modeling using flux-balance analysis identified IL-17A\u2013mediated increases in HPK glycolysis, glutaminolysis, and lipid uptake, which were validated using biochemical cell-based assays and stable isotope-resolved metabolomics. IL-17A treatment triggered downstream mitochondrial reactive oxygen species and HIF1\u03b1 expression and resultant HPK proliferation, consistent with the observed elevation of these downstream effectors in the epidermis of patients with psoriasis. Pharmacological inhibition of HIF1\u03b1 or reactive oxygen species reversed IL-17A\u2013mediated glycolysis, glutaminolysis, lipid uptake, and HPK hyperproliferation. These results identify keratinocytes as important target cells of IL-17A and reveal its involvement in multiple downstream metabolic reprogramming pathways in human skin.<\/jats:p>","DOI":"10.4049\/jimmunol.2300319","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T09:48:54Z","timestamp":1701251334000},"page":"302-316","source":"Crossref","is-referenced-by-count":31,"title":["IL-17A Orchestrates Reactive Oxygen Species\/HIF1\u03b1\u2013Mediated Metabolic Reprogramming in Psoriasis"],"prefix":"10.1093","volume":"212","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2015-2234","authenticated-orcid":false,"given":"Bhavuk","family":"Dhamija","sequence":"first","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Mumbai ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7712-6061","authenticated-orcid":false,"given":"Soumitra","family":"Marathe","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Mumbai ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6947-4026","authenticated-orcid":false,"given":"Vinanti","family":"Sawant","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Mumbai ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6691-5279","authenticated-orcid":false,"given":"Moumita","family":"Basu","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Mumbai ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diksha","family":"Attrish","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Mumbai ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7259-5520","authenticated-orcid":false,"given":"Ditipriya","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Mumbai ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7983-6761","authenticated-orcid":false,"given":"Sushant","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Mumbai ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Medha Gayathri J","family":"Pai","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Mumbai ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2398-9515","authenticated-orcid":false,"given":"Siddhi","family":"Wad","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Mumbai ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhijeet","family":"Sawant","sequence":"additional","affiliation":[{"name":"Plastic Surgery Department, Topiwala National Medical College and B.Y.L. Nair Charitable Hospital , Mumbai ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4977-1685","authenticated-orcid":false,"given":"Chitra","family":"Nayak","sequence":"additional","affiliation":[{"name":"Skin and Venereal Diseases Department, Topiwala National Medical College and B.Y.L. Nair Charitable Hospital , Mumbai ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kareenhalli V","family":"Venkatesh","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Indian Institute of Technology Bombay , Mumbai ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeeva","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Mumbai ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2107-4570","authenticated-orcid":false,"given":"Steven R","family":"Barthel","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3319-0309","authenticated-orcid":false,"given":"Rahul","family":"Purwar","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Mumbai ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,11,29]]},"reference":[{"key":"2025020405425753500_r1","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.3390\/ijms20081811","article-title":"The dynamics of the skin\u2019s immune system","volume":"20","author":"Nguyen","year":"2019","journal-title":"Int. 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