{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T19:31:45Z","timestamp":1793302305619,"version":"4.5.0"},"reference-count":88,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health\/National Institute of Allergy and Infectious Diseases","award":["1R01AI137075"],"award-info":[{"award-number":["1R01AI137075"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Multiple sclerosis (MS) is thought to be mediated by human leukocyte antigen (HLA) class II\u2013restricted autoreactive CD4 T cells producing interleukin (IL)-17A and\/or interferon \u03b3 (IFN\u03b3), but the necessity of these cytokines for disease pathogenesis is unclear. Utilizing HLA-DR3 (DR\u03b21*0301) transgenic mice lacking IFN\u03b3 or IL-17A in experimental autoimmune encephalomyelitis (EAE), a model of MS, we found that neither cytokine is essential for disease induction, although both have distinct roles. The absence of IFN\u03b3 caused atypical, brain-predominant EAE characterized by high levels of IL-17A, while the absence of IL-17A resulted in classical EAE, targeting the spinal cord. To assess whether IL-17A drives atypical EAE in the absence of IFN\u03b3, we generated HLA-DR3.IFN\u03b3\u2212\/\u2212.IL-17A\u2212\/\u2212 double knockout (DKO) mice. DKO mice developed atypical EAE with brain infiltration and inflammation of the brainstem and cerebellum, indicating that IL-17A is dispensable for brain-predominant disease in the absence of IFN\u03b3. DKO mice exhibited significant CD4 T cell infiltration and increased expression of CD4 T cell-associated genes at peak disease. Prior to central nervous system infiltration, CD4 T cell accumulated in the spleen and inguinal lymph nodes of DKO mice, where they exhibited an altered cytokine milieu and upregulated genes involved in recruitment, activation, and migration to the brain. DKO mice exhibited elevated expression of tumor necrosis factor \u03b1 (TNF\u03b1), granulocyte-macrophage colony-stimulating factor, and IL-17F; however, only TNF\u03b1 inhibition ameliorated atypical disease. Together, our findings indicate TNF\u03b1 promotes brain-predominant inflammatory pathology in the absence of IFN\u03b3 and IL-17A.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag268","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:24:15Z","timestamp":1792041855000},"source":"Crossref","is-referenced-by-count":0,"title":["TNF\u03b1 promotes brain-predominant EAE independent of IFN\u03b3 and IL-17A in HLA-DR3 transgenic mice"],"prefix":"10.1093","volume":"215","author":[{"given":"Ti-Ara J","family":"Turner","sequence":"first","affiliation":[{"name":"Immunology Graduate Program, University of Iowa , Iowa City, IA,","place":["United States"]},{"name":"Department of Pathology, University of Iowa , Iowa City, IA,","place":["United States"]},{"name":"Iowa City VA Healthcare System , Iowa City, IA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie R","family":"Peterson","sequence":"additional","affiliation":[{"name":"Immunology Graduate Program, University of Iowa , Iowa City, IA,","place":["United States"]},{"name":"Department of Pathology, University of Iowa , Iowa City, IA,","place":["United States"]},{"name":"Iowa City VA Healthcare System , Iowa City, IA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian E","family":"Alt","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa , Iowa City, IA,","place":["United States"]},{"name":"Iowa City VA Healthcare System , Iowa City, IA,","place":["United States"]},{"name":"College of Liberal Arts and Sciences, University of Iowa , Iowa City, IA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leeann S","family":"Aguilar Meza","sequence":"additional","affiliation":[{"name":"Holden Comprehensive Cancer Center, University of Iowa , Iowa City, IA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1552-3253","authenticated-orcid":false,"given":"David K","family":"Meyerholz","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa , Iowa City, IA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shailesh K","family":"Shahi","sequence":"additional","affiliation":[{"name":"Immunology Graduate Program, University of Iowa , Iowa City, IA,","place":["United States"]},{"name":"Department of Pathology, University of Iowa , Iowa City, IA,","place":["United States"]},{"name":"Iowa City VA Healthcare System , Iowa City, IA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9926-2531","authenticated-orcid":false,"given":"Ashutosh K","family":"Mangalam","sequence":"additional","affiliation":[{"name":"Immunology Graduate Program, University of 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