Molecular Pathogenesis Program, Helen and Martin Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, Department of Pathology, New York University School of Medicine, New York, NY 10016, USA.
Trends Immunol. 2011 Aug;32(8):358-63. doi: 10.1016/j.it.2011.04.007. Epub 2011 Jul 4.
Protein kinase C (PKC)-θ regulates conventional effector T (Teff) cell function. Since this initial finding, it has become clear that the role of PKC-θ in T cells is complex. PKC-θ plays a central role in Teff cell activation and survival, and negatively regulates stability of the immunological synapse (IS). Recent studies demonstrated that PKC-θ is required for the development of natural CD4(+)Foxp3(+) regulatory T (Treg) cells, and mediates negative regulation of Treg cell function. Here, we examine the role of PKC-θ in the IS, evidence for its distinct localization in Treg cells and the therapeutic implications of inhibiting PKC-θ in Teff cells, to reduce effector function, and in Treg cells, to increase suppressor function, for the prevention and treatment of autoimmune and alloimmune disease states.
蛋白激酶 C（PKC）-θ 调节常规效应 T（Teff）细胞功能。自最初的发现以来，PKC-θ 在 T 细胞中的作用已变得清晰复杂。PKC-θ 在 Teff 细胞的激活和存活中起核心作用，并负调节免疫突触（IS）的稳定性。最近的研究表明，PKC-θ 是天然 CD4（+）Foxp3（+）调节性 T（Treg）细胞发育所必需的，并且介导 Treg 细胞功能的负调节。在这里，我们研究了 PKC-θ 在 IS 中的作用，证明其在 Treg 细胞中的独特定位及其在抑制 Teff 细胞中的 PKC-θ 以减少效应功能，以及在 Treg 细胞中抑制 PKC-θ 以增加抑制功能方面的治疗意义，用于预防和治疗自身免疫和同种免疫疾病状态。
