Journal Article

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

Bhargava, Rhea, Tsokos, George C., Tsokos, Maria G., Ferretti, Andrew P., Dahan, Shani

2018

Overview

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.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Antigen-antibody complexes / Antigens / Autoimmunity / Ca2+/calmodulin-dependent protein kinase / calcium/calmodulin kinase IV / Calmodulin / CaMK4 / CD4 antigen / Cell growth / Cell proliferation / IL-17 / IL-2 deprivation / Immunology / Kinases / Lupus / Lupus nephritis / Lymphocytes / Lymphocytes T / Mesangial cells / Pathogenesis / Pathology / Phosphorylation / podocyte dysfunction / Proteins / Regulation / Structure-function relationships / Systemic lupus erythematosus / T cell receptors / Transcription factors / Treg deficiency