Calcium calmodulin kinase IV deficiency in podocytes prevents the development of lupus nephritis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread organ involvement including the kidney. Calcium/calmodulin-dependent protein kinase IV (CaMK4) has been shown to conrol immune cell nad podocyte function. To address the effect of genetic podocyte-specific CaMK4 deficiency on systemic autoimmunity and kidney pathology in lupus-prone mice we generated B6.

Injury pattern of feet and lower limbs in a feet-first fall from height.

In fatalities caused by falls from height, the analysis of the injury pattern, alongside with circumstantial data, is crucial for understanding the dynamics of the incident. In rare cases, even a differentiation between accidental and intentional events might be possible. The injury pattern of the lower limbs is particularly significant in this context.

CD38 in SLE CD4 T cells promotes Ca flux and suppresses interleukin-2 production by enhancing the expression of GM2 on the surface membrane.

CD38 has emerged as a potential therapeutic target for patients with systemic lupus erythematosus (SLE) but it is not known whether CD38 alters CD4 T cell function. Using primary human T cells and CD38-sufficient and CD38-deficient Jurkat T cells, we demonstrate that CD38 shifts the T cell lipid profile of gangliosides from GM3 to GM2 by upregulating B4GALNT1 in a Sirtuin 1-dependent manner. Enhanced expression of GM2 causes ER stress by enhancing Ca flux through the PLCγ1-IP3 pathway.

The PP2A regulatory subunit PPP2R2A controls NAD biosynthesis to regulate T cell subset differentiation in systemic autoimmunity.

The protein phosphatase 2A (PP2A) regulatory subunit PPP2R2A is involved in the regulation of immune response. We report that lupus-prone mice with T cells deficient in PPP2R2A display less autoimmunity and nephritis. PPP2R2A deficiency promotes NAD biosynthesis through the nicotinamide riboside (NR)-directed salvage pathway in T cells.

CaMK4 controls follicular helper T cell expansion and function during normal and autoimmune T-dependent B cell responses.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by dysregulated B cell compartment responsible for the production of autoantibodies. Here, we show that T cell-specific expression of calcium/calmodulin-dependent protein kinase IV (CaMK4) leads to T follicular helper (T) cells expansion in models of T-dependent immunization and autoimmunity. Mechanistically, CaMK4 controls the T-specific transcription factor B cell lymphoma 6 (Bcl6) at the transcriptional level through the cAMP responsive element modulator α (CREMα).