Abstract
Autoimmune diseases generally result from the loss of self-tolerance (i.e., failure of the immune system to distinguish self from non-self), and are characterized by autoantibody production and hyperactivation of T cells, which leads to damage of specific or multiple organs. Thus, autoimmune diseases can be classified as organ-specific or systemic. Genetic and environmental factors contribute to the development of autoimmunity. Recent studies have demonstrated the contribution of innate immunity to the onset of autoimmune diseases. Natural killer (NK) cells, which are key components of the innate immune system, have been implicated in the development of multiple autoimmune diseases such as systemic lupus erythematosus, type I diabetes mellitus, and autoimmune liver disease. However, NK cells have both protective and pathogenic roles in autoimmunity depending on the NK cell subset, microenvironment, and disease type or stage. In this work, we review the current knowledge of the varied roles of NK cell subsets in systemic and organic-specific autoimmune diseases and their clinical potential as therapeutic targets.
Highlights
Autoimmune diseases generally result from the loss of self-tolerance, which leads to the production of autoantibodies and self-reactive lymphocytes that cause tissue damage [1, 2]
CD27−, CD127−, and CXCR3− natural killer (NK) cells have potent cytotoxicity resembling that of CD56dim NK cells in humans, whereas NK cells positive for these markers are responsible for cytokine secretion and have low cytolytic capacity like the human CD56bright subset
It was further demonstrated that DX5−CD11chi lrNK cells colocalized with and inhibited the proliferation of CD4+ T cells [143]. These findings strongly suggest that liver-infiltrating NK cells participate in autoimmune liver disease (ALD) development, the detailed mechanisms require further investigation
Summary
Autoimmune diseases generally result from the loss of self-tolerance (i.e., failure of the immune system to distinguish self from non-self), which leads to the production of autoantibodies and self-reactive lymphocytes that cause tissue damage [1, 2]. Most autoimmune diseases are relatively uncommon, they are associated with significant morbidity and mortality. Autoimmune diseases principally develop as a result of abnormal activation of T and B cells. There is increasing evidence that natural killer (NK) cells—which link innate and adaptive immunity—play an important role in their development, for example in SLE, type 1 diabetes mellitus (T1DM), and autoimmune liver disease (ALD) [5,6,7]. NK cell activation is governed by the integration of activating and inhibitory signals from cell surface receptors [9, 10]; NK cells detect cells that are under stress as a result of infection or malignancy and rapidly respond by secreting cytotoxic granules or death receptor ligands
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