Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Front Immunol. 2018 Oct 1;9:2113. doi: 10.3389/fimmu.2018.02113. eCollection 2018.
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.
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，调节多种对狼疮相关病理学有重大贡献的过程。在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 破坏足细胞的结构和功能。在狼疮易感小鼠中，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，而不影响狼疮易感小鼠中的自身免疫，并避免阿霉素诱导的正常小鼠的病理。因此，将 CaMK4 抑制剂靶向递送至足细胞具有很高的治疗免疫性（狼疮性肾炎）和非免疫性（FSGS）足细胞病的潜力。
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