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Th1 effector CD4 T cells rely on IFN-g production to induce Alopecia areata

ABSTRACT: Alopecia areata (AA) is an autoimmune disease that is characterized by hair loss clinically and peribulbar infiltration of CD8 and CD4 T cells histologically. Prior studies have focused on the role of CD8 T cells in the development of AA; however, the role of CD4 T cells is unclear. Here, we demonstrate that CD4 T cells from the skin draining lymph nodes (SDLN) of AA mice could transfer disease into recipient mice. Further, these cells exhibited a T-helper type 1 (Th1) effector transcriptional and phenotypic profile. Pathogenic activity of these CD4 T cells was dependent upon the presence of endogenous CD8 T cells and host IFN-g signaling. Targeted removal of CD4 T cell-mediated production of IFN-g abrogated the ability of this cell population to transfer disease. Together, our study provides mechanistic insights into pathways that lead to AA development, heightening our understanding of the disease and inviting studies into exploring novel therapeutic strategies for human patients.

ORGANISM(S): Mus musculus

PROVIDER: GSE295313 | GEO | 2025/09/23

REPOSITORIES: GEO

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Project description:Background/Purpose: Systemic lupus erythematosus (SLE) is a complex multi-system autoimmune disease of uncertain etiology. Patients from different ancestral backgrounds demonstrate differences in clinical manifestations and autoantibody profiles. In this study we examined genome-wide transcriptional patterns in major immune cell subsets across different ancestral backgrounds. Methods: Peripheral blood was collected from 21 African-American (AA) and 21 European-American (EA) SLE patients, 5 AA controls, and 5 EA controls. CD4+ T-cells, CD8+ T-cells, monocytes and B cells were purified by flow sorting. Each cell subset from each subject was run on an Illumina HumanHT-12 V4 expression BeadChip array (n=208 arrays). Differentially expressed genes (DEGs) were determined by comparing cases and controls of the same ancestral background. Results: The overlap in DEG lists between different cell types from the same ancestral background was very modest (<1%). Typically between 5-10% of DEGs were shared when comparing the same cell type between different ancestral backgrounds (for ex. CD20 AA vs. CD20 EA). Quantitative measurement of global IFN-stimulated gene (ISG) expression revealed that AA subjects demonstrated more concordance across all studied cell types. Two subgroups of patients were identified based on the ISG expression profiles. One subgroup showed higher ISGs expression in all cell types, and the other subgroup had higherISG expression only in T and B lymphocytes but not in monocytes. The correlation of ISG expression with medication data revealed that only the B cells had lower ISG expression in patients taking immunosuppressants, while ISG expression in the other cell types did not differ based upon medication use. Conclusion: We find striking differences in gene expression between different immune cell subsets and between ancestral backgrounds in SLE patients. The IFN signature is diverse, with different transcripts represented in different cell populations, and signature-positive cell subsets differed in EA vs. AA patients. We also find that treatment with the immunosuppressive agents correlates with the down-regulation of B cell ISG expression, and this was not observed in other cell types. Peripheral blood was collected from 21 African-American (AA) and 21 European-American (EA) SLE patients, 5 AA controls, and 5 EA controls. CD4+ T-cells, CD8+ T-cells, monocytes and B cells were purified by flow sorting. Each cell subset from each subject was run on an Illumina HumanHT-12 V4 expression BeadChip array (n=208 arrays).

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Th1 effector CD4 T cells rely on IFN-g production to induce Alopecia areata

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