title: Autoimmune regulator‑overexpressing dendritic cells induce T helper 1 and T helper 17 cells by upregulating cytokine expression.
abstract: The autoimmune regulator (Aire) protein is a transcriptional activator that is essential in central immune tolerance, as it regulates the ectopic expression of many tissue‑restricted antigens in medullary thymic epithelial cells. Aire expression has also been described in hematopoietic cells, such as monocytes/macrophages and dendritic cells (DCs), in the peripheral immune system. However, the role of Aire expression in peripheral immune system cells, including DCs, remains to be elucidated. In the present study, the effects of secreted cytokines from Aire‑overexpressing DCs on cluster of differentiation (CD)4+ T cell subsets were investigated. The dendritic cell line, DC2.4, which overexpresses Aire, was co‑cultured with CD4+ T cells from splenocytes using Transwell inserts. The results indicate that Aire‑overexpressing cells induce T helper (Th)1 subsets by increasing interleukin (IL)‑12 expression, and induce Th17 subsets by upregulating IL‑6 and transforming growth factor (TGF)‑β production. In addition, it was observed that increased levels of phosphorylated extracellular signal‑regulated kinases and p38 upregulated the expression of cytokines in Aire‑overexpressing cells. These data suggest that Aire may have a role in inducing Th1 and Th17 differentiation by upregulating cytokine expression in DCs.
authors.affiliation: Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Dongbei
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Jitong
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D018920:Coculture Techniques; D016207:Cytokines; D003713:Dendritic Cells / Q000378:metabolism*; D005434:Flow Cytometry; D020935:MAP Kinase Signaling System; D008297:Male; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D018417:Th1 Cells / Q000378:metabolism*; D058504:Th17 Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation; D000096927:AIRE Protein
chemical_list: D016207:Cytokines; D014157:Transcription Factors; D000096927:AIRE Protein