Abstract
Natural killer T (NKT) cells are a distinct lineage of T cells which express both the T cell receptor (TCR) and natural killer (NK) cell markers. Invariant NKT (iNKT) cells bear an invariant TCR and recognize a small variety of glycolipid antigens presented by CD1d (nonclassical MHC-I). CD1d-restricted iNKT cells are regulators of immune responses and produce cytokines that may be proinflammatory (such as interferon-gamma (IFN-γ)) or anti-inflammatory (such as IL-4). iNKT cells also appear to play a role in B cell regulation and antibody production. Alpha-galactosylceramide (α-GalCer), a derivative of the marine sponge, is a potent stimulator of iNKT cells and has been proposed as a therapeutic iNKT cell activator. Invariant NKT cells have been implicated in the development and perpetuation of several autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus (SLE). Animal models of SLE have shown abnormalities in iNKT cells numbers and function, and an inverse correlation between the frequency of NKT cells and IgG levels has also been observed. The role of iNKT cells in autoimmune liver disease (AiLD) has not been extensively studied. This review discusses the current data with regard to iNKT cells function in AiLD, in addition to providing an overview of iNKT cells function in other autoimmune conditions and animal models. We also discuss data regarding the immunomodulatory effects of vitamin D on iNKT cells, which may serve as a potential therapeutic target, given that deficiencies in vitamin D have been reported in various autoimmune disorders.
Highlights
Natural killer T (NKT) cells are a component of the innate immune system, which initiate and refine innate and adaptive immune responses
NKT cells can be subdivided into type 1 and type 2 NKT cells based on their T cell receptors (TCR), with type 1 NKT cells being commonly known as invariant NKT cells [1,2,3]
De Santo et al have demonstrated that the absence of invariant NKT cells in mice during Influenza IAV infection resulted in the expansion of myeloid derived suppressor cells (MDSCs), which suppressed IAV-specific immune responses through the expression of both arginase and NOS, resulting in high IAV titer and increased mortality [133]
Summary
Natural killer T (NKT) cells are a component of the innate immune system, which initiate and refine innate and adaptive immune responses. A variety of innate lymphocytic populations, including NKT cells, γδ T cells, mucosalassociated invariant T cells, and CD56(+) natural killer (NK) cells are resident or can rapidly accumulate in the hepatic microenvironment following potential pathogenic challenge [7, 8]. These cells can maintain or override hepatic immune tolerance to autoantigens, leading to expansion of autoreactive T cells that mediate liver injury causing autoimmune liver disease or direct liver injury by killing hepatocytes or bile duct cells [9, 10]. We will discuss the emerging role of vitamin D in iNKT cells immunomodulation, which may serve as a therapeutic target [44,45,46]
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