Mechanisms of EAE in the Absence of IFNg and IL-17A: Insights from HLA-DR3 Transgenic Mice 4300

Ti-Ara J. Turner; Stephanie Peterson; Lian Alt; Leeann Aguilar-Meza; Shailesh K. Shahi; Ashutosh K. Mangalam

doi:10.1093/jimmun/vkaf283.2000

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Mechanisms of EAE in the Absence of IFNg and IL-17A: Insights from HLA-DR3 Transgenic Mice 4300

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Mechanisms of EAE in the Absence of IFNg and IL-17A: Insights from HLA-DR3 Transgenic Mice 4300

Ti-Ara J. Turner, Stephanie Peterson, Lian Alt, Leeann Aguilar-Meza, Shailesh K. Shahi and Ashutosh K. Mangalam

The Journal of immunology (1950), Vol.214(Supplement_1), vkaf2832000

11/01/2025

DOI: 10.1093/jimmun/vkaf283.2000

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Abstract

Abstract Description Multiple sclerosis (MS) is thought to be mediated by HLA class-II restricted, IL-17A and IFNg producing, autoreactive CD4 T cells. However, their exact role in disease development is unclear. To investigate these cytokines, we immunized HLA-DR3 (DRB1*0301) transgenic mice deficient in IFNg or IL-17A to induce experimental autoimmune encephalomyelitis (EAE), a model of MS. Our results show that neither cytokine is essential for disease induction, but both influence disease presentation. Without IFNg, mice developed atypical, brain-specific EAE with elevated IL-17A levels, while lack of IL-17A led to classical, spinal cord-specific EAE with increased Treg cells and Treg-enriching gut microbiota. To assess the combined role of both cytokines, we created HLA-DR3.IFNg -/-IL-17A-/- double knockout (DKO) mice. DKO mice developed atypical EAE marked by increased CD45+ cell infiltration in the brain, along with inflammation and demyelination in the brainstem and cerebellum. DKO mice exhibited significant Th17 (CD4+RORgT+) cell infiltration in the brain, 25 days after immunization. Before Th17 cells infiltrated the CNS, they were significantly recruited to the spleen and draining lymph nodes, where they upregulated genes involved in migration and activation (Il-17f, Rorc, Ccr6, Il21, and Il22). These findings suggest that Th17 cells contribute to disease in the absence of IFNg and IL-17A. Future studies will explore the functions of Th17 cells in DKO mice.

Cells - T Cells Diseases - EAE/MS Molecules - Cytokines Processes - Neuroimmunology

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Title: Subtitle: Mechanisms of EAE in the Absence of IFNg and IL-17A: Insights from HLA-DR3 Transgenic Mice 4300
Creators: Ti-Ara J. Turner
Stephanie Peterson - University of California, Riverside
Lian Alt - University of Iowa
Leeann Aguilar-Meza - University of Iowa Holden Comprehensive Cancer Center
Shailesh K. Shahi
Ashutosh K. Mangalam
Resource Type: Abstract
Publication Details: The Journal of immunology (1950), Vol.214(Supplement_1), vkaf2832000
DOI: 10.1093/jimmun/vkaf283.2000
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: Oxford University Press
Grant note: NIH T32 Training Grant: T32AI007485 University of Iowa Sloan Mini GrantVA Merit Awards: 1I01CX002212, I01BX006112
Supported by NIH T32 Training Grant T32AI007485 (to Kevin Legge); University of Iowa Sloan Mini Grant (to T.J.T.); VA Merit Awards: 1I01CX002212 and I01BX006112 (to A. K.M,); a gift from P. Heppelmann and M. Wacek (to A.K.M) Topic Categories: Neuroimmunology (NEUR)
Alternative title: IMMUNOLOGY2025™ Abstracts
Language: English
Date published: 11/01/2025
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9985034936502771

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