Background and aims Apoptosis is a genetically conserved pathway and a regular feature in normal tissue homeostasis.Aberrant cell apoptosis could result in imbalanced immune regulation and plays an important role in the development of autoimmune diseases, especially in systemic lupus erythematosus(SLE).
Methods SLE is a complex,multisystem autoimmune disease characterised by production of high-titer autoantibodies directed against tissue-specific and ubiquitously expressed self-antigens. There has been greatly confirmed that accelerated cell apoptosis and apoptotic debris could account for the accumulation of a great deal of nuclear antigens, which could be presented to antigen presenting cells and lymphocytes,and subsequently induce incomplete immune tolerance,potentially through abnormal apoptotic signalling pathways and abnormal signalling thresholds on responding lymphocytes.Impaired clearance of apoptotic cells is also likely to be an important factor in SLE pathogenesis, which is originated from morphIncreasedological abnormalities, impaired differentiating and adhesion ability of macrophage cells, abnormal chemokines and phagecytosis-related receptors expression and lack of complements.
Results The dysfunction of apoptosis may be a direct consequence of alterations in genes such as Fas, Bcl-2 and C1q. Increased expression of Fas antigen could intensify the exposure of hidden antigens. The overexpression of Bcl-2 protein might inhibit the removal of auto-reactive cells, and the lack of C1q could impair the clearance of self-antigens.Increased apoptosis of lymphcytes especially regulatory T cells is also an important reason to lead to breakdown of immuntolerance.
Conclusions The complete knowledge of the role of apoptosis components in the etiopathogenesis of lupus could lead to the development of new therapies targeting the apoptotic threshold, which could result in a more specific and effective disease response compared to global immunosuppression.
- © 2017, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions
Statistics from Altmetric.com
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.