文章基本信息

标题：Human in vitro-induced regulatory T cells display Dlgh1dependent and PKC-θ restrained suppressive activity
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作者：Alexandra Zanin-Zhorov ; Sudha Kumari ; Keli L. Hippen 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
DOI：10.1038/s41598-017-04053-5
语种：English
出版社：Springer Nature
摘要：In vitro induced human regulatory T cells (iTregs) have demonstrated in vivo therapeutic utility, but pathways regulating their function have not been elucidated. Here, we report that human iTregs generated in vitro from naïve cord blood cells preferentially recruit Disc large homolog 1 (Dlgh1) and exclude protein kinase C (PKC)-θ from immunological synapses formed on supported lipid bilayers with laterally mobile ICAM-1 and anti-CD3 mAb. Also, iTregs display elevated Dlgh1 overall and Dlgh1-dependent p38 phosphorylation, higher levels of phosphatase and tensin homolog (PTEN), and diminished Akt phosphorylation. Pharmacological interruption of PKC-θ increases and Dlgh1 silencing decreases the ability of iTregs to suppress interferon-γ production by CD4(+)CD25(-) effector T cells (Teff). Comparison with expanded cord blood-derived CD4(+)CD25(hi) tTreg and expanded Teffs from the same donors indicate that iTreg are intermediate between expanded CD4(+)CD25(hi) tTregs and Teffs, whereas modulation of suppressive activities by PKC-θ and Dlgh1 signaling pathways are shared.