title: Macrophages overexpressing Aire induce CD4+Foxp3+ T cells.
abstract: Aire plays an important role in central immune tolerance by regulating the transcription of thousands of genes. However, the role of Aire in the peripheral immune system is poorly understood. Regulatory T (Treg) cells are considered essential for the maintenance of peripheral tolerance, but the effect of Aire on Treg cells in the peripheral immune system is currently unknown. In this study, we investigated the effects of macrophages overexpressing Aire on CD4+Foxp3+ Treg cells by co-culturing Aire-overexpressing RAW264.7 cells or their supernatant with splenocytes. The results show that macrophages overexpressing Aire enhanced the expression of Foxp3 mRNA and induced different subsets of Treg cells in splenocytes through cell-cell contact or a co-culture supernatants. TGF-β is a key molecule in the increases of CD4+CD45RA+Foxp3hi T cell and activating Treg (aTreg) levels observed following cell‑supernatant co-culturing. Subsets of Treg cells were induced by Aire-overexpressing macrophages, and the manipulation of Treg cells by the targeting of Aire may provide a method for the treatment of inflammatory or autoimmune diseases.
authors.affiliation: Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun, PR China.
authors.forename: Jitong
authors.initials: J
authors.lastname: Sun
authors.forename: Haiying
authors.initials: H
authors.lastname: Fu
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Wufei
authors.initials: W
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D000096927:AIRE Protein
chemical_list: D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000096927:AIRE Protein; C498833:Foxp3 protein, mouse