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AI-24 Calcium/calmodulin kinase controls T and renal cell function
  1. George C Tsokos
  1. Harvard Medical School, Beth Israel Deaconess Medical Centre, Boston, MA


Background Molecular abnormalities in SLE T cells account for their aberrant function including cytokine production, cytotoxic responses and help to B cells.

Materials and methods Use of biochemical, molecular biology and engineered mice; study of kidney tissues and isolated kidney cells.

Results Calcium calmodulin kinase IV (CaMK4) is expressed at high levels in T cells from patients with SLE and accounts for the decreased production of IL-2 and the increased production of il-17. The mechanisms involved modification of transcription factors and epigenetic changes. CaMK4 drives proliferation of mesangial cells in lupus prone mice and the production of IL-6. In parallel CaMK4 suppresses the expression of nephrin in podocytes resulting in proteinuria and also advances the expression of CD86 enabling thus podocytes to provide costimulation to passer-by T cells. Targeted delivery of a CaMK4 inhibitor to CD4 T cells reverses autoimmunity in lupus-prone mice.

Conclusions CaMK4 accounts for the abnormal production of cytokines by SLE T cells, the proliferation of mesangial cells and the poor function of podocytes. Targeting CaMK4 and targeted delivery of CaMK4 inhibitors to T cells has proven promising in preclinical studies.

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