Calcium/Calmodulin Kinase IV Controls the Function of Both T Cells and Kidney Resident Cells.

Calcium/Calmodulin Kinase IV Controls the Function of Both T Cells and Kidney Resident Cells.
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DOI:
10.3389/fimmu.2018.02113
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发表时间:
2018
影响因子:
7.3
通讯作者:
Tsokos GC
Tsokos GC
中科院分区:
医学2区
文献类型:
--
作者:
Ferretti AP;Bhargava R;Dahan S;Tsokos MG;Tsokos GC

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钙调蛋白激酶 IV (CaMK4) 通过控制 T 细胞产生 IL-2 和 IL-17、系膜细胞增殖以及足细胞的功能和结构,调节多个过程,从而显着促进狼疮相关病理。局灶节段性肾小球硬化症 (FSGS) 患者的足细胞中 CaMK4 也上调。在免疫性和非免疫性足细胞病中,CaMK4 会破坏足细胞的结构和功能。在易患狼疮的小鼠中,将 CaMK4 抑制剂靶向递送至 CD4+ T 细胞可抑制自身免疫和肾炎的发展。靶向递送至足细胞可避免免疫复合物的沉积,而不影响狼疮易发小鼠的自身免疫,并避免阿霉素在正常小鼠中诱导的病理。因此,将 CaMK4 抑制剂靶向递送至足细胞对于免疫性(狼疮性肾炎)和非免疫性 (FSGS) 足细胞病具有很高的治疗前景。
Calcium calmodulin kinase IV (CaMK4) regulates multiple processes that significantly contribute to the lupus-related pathology by controlling the production of IL-2 and IL-17 by T cells, the proliferation of mesangial cells, and the function and structure of podocytes. CaMK4 is also upregulated in podocytes from patients with focal segmental glomerulosclerosis (FSGS). In both immune and non-immune podocytopathies, CaMK4 disrupts the structure and function of podocytes. In lupus-prone mice, targeted delivery of a CaMK4 inhibitor to CD4+ T cells suppresses both autoimmunity and the development of nephritis. Targeted delivery though to podocytes averts the deposition of immune complexes without affecting autoimmunity in lupus-prone mice and averts pathology induced by adriamycin in normal mice. Therefore, targeted delivery of a CaMK4 inhibitor to podocytes holds high therapeutic promise for both immune (lupus nephritis) and non-immune (FSGS) podocytopathies.
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