Calcineurin and Systemic Lupus Erythematosus: The Rationale for Using Calcineurin Inhibitors in the Treatment of...

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a broad spectrum of clinical presentations that can affect almost all organ systems. Lupus nephritis (LN) is a severe complication that affects approximately half of the systemic erythematosus lupus (SLE) patients, which significantly increases the morbidity and the mortality risk. LN is characterized by the accumulation of immune complexes, ultimately leading to renal failure. Aberrant activation of T cells plays a critical role in the pathogenesis of both SLE and LN and is involved in the production of inflammatory cytokines, the recruitment of inflammatory cells to the affected tissues and the co-stimulation of B cells. Calcineurin is a serine-threonine phosphatase that, as a consequence of the T cell hyperactivation, induces the production of inflammatory mediators. Moreover, calcineurin is also involved in the alterations of the podocyte phenotype, which contribute to proteinuria and kidney damage observed in LN patients. Therefore, calcineurin inhibitors have been postulated as a potential treatment strategy in LN, since they reduce T cell activation and promote podocyte cytoskeleton stabilization, both being key aspects in the development of LN. Here, we review the role of calcineurin in SLE and the latest findings about calcineurin inhibitors and their mechanisms of action in the treatment of LN.