{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:04:19Z","timestamp":1791374659485,"version":"4.3.1"},"reference-count":69,"publisher":"National Academy of Sciences","issue":"32","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI144004"],"award-info":[{"award-number":["AI144004"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS112727"],"award-info":[{"award-number":["NS112727"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["RG-2111-38733"],"award-info":[{"award-number":["RG-2111-38733"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Henry Ford Hospital","award":["A10270 A30967"],"award-info":[{"award-number":["A10270 A30967"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,8,12]]},"abstract":"<jats:p>\n                    Pathogenic Th17 cells play crucial roles in CNS autoimmune diseases such as multiple sclerosis (MS), but their regulation by endogenous mechanisms remains unknown. Through RNA-seq analysis of primary brain glial cells, we identified immune-responsive gene 1 (\n                    <jats:italic toggle=\"yes\">Irg1<\/jats:italic>\n                    ) as one of the highly upregulated genes under inflammatory conditions. Validation in the spinal cords of animals with experimental autoimmune encephalomyelitis (EAE), a preclinical MS model, confirmed elevated\n                    <jats:italic toggle=\"yes\">Irg1<\/jats:italic>\n                    levels in myeloid, CD4, and B cells in the EAE group, raising concerns as to whether\n                    <jats:italic toggle=\"yes\">Irg1<\/jats:italic>\n                    is detrimental or protective.\n                    <jats:italic toggle=\"yes\">Irg1<\/jats:italic>\n                    knockout (KO) mice exhibited severe EAE disease, increased mononuclear cell infiltration, and increased levels of triple-positive CD4+ T cells expressing IL17a, GM-CSF, and IFN\u03b3. Adoptive transfer in Rag-1 KO and single-cell RNA sequencing highlighted the crucial role of\n                    <jats:italic toggle=\"yes\">Irg1<\/jats:italic>\n                    in shaping pathogenic Th17 cells. A lack of\n                    <jats:italic toggle=\"yes\">Irg1<\/jats:italic>\n                    in macrophages elevates Class II expression, promoting the polarization of myelin-primed CD4+ T cells into pathogenic Th17 cells via the NLRP3\/IL-1\u03b2 axis. Moreover, bone marrow chimeras revealed that immune cells lacking\n                    <jats:italic toggle=\"yes\">Irg1<\/jats:italic>\n                    maintained pathogenic and inflammatory phenotypes, suggesting its protective role in autoimmune diseases, including MS.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2427052122","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T19:05:07Z","timestamp":1754334307000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["Immune-responsive gene 1: The mitochondrial key to Th17 cell pathogenicity in CNS autoimmunity"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8393-6717","authenticated-orcid":false,"given":"Mohammad","family":"Nematullah","sequence":"first","affiliation":[{"name":"Department of Neurology, Henry Ford Health 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Neurology, Henry Ford Health System","place":["Detroit"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kameshwar","family":"Ayasolla","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henry Ford Health System","place":["Detroit"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Ejaz","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henry Ford Health System","place":["Detroit"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruicong","family":"She","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Henry Ford Health System","place":["Detroit"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajad","family":"Mir","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henry Ford Health System","place":["Detroit"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9919-1959","authenticated-orcid":false,"given":"Insha","family":"Zahoor","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henry Ford Health System","place":["Detroit"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasrul","family":"Hoda","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henry Ford Health System","place":["Detroit"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramandeep","family":"Rattan","sequence":"additional","affiliation":[{"name":"Division of Gynecology Oncology, Department of Women\u2019s Health Services, Henry Ford 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Nematullah Immune-responsive gene 1: The mitochondrial key to Th17 cell pathogenicity in CNS autoimmunity. Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE298306. 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