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蛋白激酶Cθ对于CD25 + CD4 +调节性T细胞介导的抑制作用是可有可无的。

Protein kinase C theta is dispensable for suppression mediated by CD25+CD4+ regulatory T cells.

作者信息

Siegmund Kerstin, Thuille Nikolaus, Wachowicz Katarzyna, Hermann-Kleiter Natascha, Baier Gottfried

机构信息

Department for Pharmacology and Genetics, Medical University Innsbruck, Innsbruck, Austria.

出版信息

PLoS One. 2017 May 22;12(5):e0175463. doi: 10.1371/journal.pone.0175463. eCollection 2017.

Abstract

The activation of conventional T cells upon T cell receptor stimulation critically depends on protein kinase C theta (PKCθ). However, its role in regulatory T (Treg) cell function has yet to be fully elucidated. Using siRNA or the potent and PKC family-selective pharmacological inhibitor AEB071, we could show that murine Treg-mediated suppression in vitro is independent of PKCθ function. Likewise, Treg cells of PKCθ-deficient mice were fully functional, showing a similar suppressive activity as wild-type CD25+CD4+ T cells in an in vitro suppression assay. Furthermore, in vitro-differentiated wild-type and PKCθ-deficient iTreg cells showed comparable Foxp3 expression as well as suppressive activity. However, we observed a reduced percentage of Foxp3+CD25+ CD4+ T cells in the lymphatic organs of PKCθ-deficient mice. Taken together, our results suggest that while PKCθ is involved in Treg cell differentiation in vivo, it is dispensable for Treg-mediated suppression.

摘要

传统T细胞在T细胞受体刺激下的激活关键取决于蛋白激酶Cθ(PKCθ)。然而,其在调节性T(Treg)细胞功能中的作用尚未完全阐明。使用小干扰RNA(siRNA)或强效且对PKC家族具有选择性的药理抑制剂AEB071,我们能够证明小鼠Treg细胞在体外介导的抑制作用独立于PKCθ功能。同样,PKCθ缺陷小鼠的Treg细胞功能完全正常,在体外抑制试验中表现出与野生型CD25 + CD4 + T细胞相似的抑制活性。此外,体外分化的野生型和PKCθ缺陷诱导性Treg(iTreg)细胞表现出相当的Foxp3表达以及抑制活性。然而,我们观察到PKCθ缺陷小鼠淋巴器官中Foxp3 + CD25 + CD4 + T细胞的百分比降低。综上所述,我们的结果表明,虽然PKCθ参与体内Treg细胞的分化,但它对于Treg介导的抑制作用是可有可无的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8600/5439664/20897c60335e/pone.0175463.g001.jpg

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