期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/ijms22031263
关键词
lupus nephritis; calcineurin; T cells; clinical trial; therapeutic target
资金
- Xunta de Galicia [IN606A-2020/043]
- Miguel Servet program from the Instituto de Salud Carlos III (ISCIII) [CP19/00005]
- European Social Fund (Investing in your future)
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect almost all organ systems, with lupus nephritis (LN) being a severe complication affecting approximately half of SLE patients. LN is characterized by the accumulation of immune complexes leading to renal failure. Aberrant T cell activation plays a critical role in the pathogenesis of both SLE and LN.
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.
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