Article Text

PDF

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

Abstract

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.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.