Abstract
Innate-like T cells such as invariant natural killer T (iNKT) cells and mucosal-associated T (MAIT) cells, characterized by a semi-invariant T cell receptor and restriction toward MHC-like molecules (CD1 and MR1 respectively), are a unique unconventional immune subset acting at the interface of innate and adaptive immunity. Highly represented at barrier sites and capable of rapidly producing substantial amounts of cytokines, they serve a pivotal role as first-line responders against microbial infections. In contrast, it was demonstrated that innate-like T cells can be skewed toward a predominant pro-inflammatory state and are consequently involved in a number of autoimmune and inflammatory diseases like inflammatory bowel diseases and rheumatic disorders, such as spondyloarthritis (SpA) and rheumatoid arthritis. Interestingly, there is link between gut and joint disease as they often co-incide and share certain aspects of the pathogenesis such as established genetic risk factors, a critical role for pro-inflammatory cytokines, such as TNF-α, IL-23, and IL-17 and therapeutic susceptibility. In this regard dysregulated IL-23/IL-17 responses appear to be crucial in both debilitating pathologies and innate-like T cells likely act as key player. In this review, we will explore the remarkable features of iNKT cells and MAIT cells, and discuss their contribution to immunity and combined gut–joint disease.
Highlights
Over the past decades, innate-like T cells have gained increasing attention given their unique biology and potential involvement in multiple immune and inflammatory diseases
After believing for a long time that solely MHC–peptide complexes can be recognized by T cells, it is known that T cell receptor (TCR) can bindlipid, vitamin metabolites, and other non-peptidic antigens
To direct activation by recognizing microbial-derived ligands via their semi-invariant TCR, they can be activated indirectly, upon which they respond by rapidly producing copious amounts of effector molecules as a first-line defense making them excellent gatekeepers against potential invasive pathogens [36, 97]
Summary
Innate-like T cells have gained increasing attention given their unique biology and potential involvement in multiple immune and inflammatory diseases. In RA, there is a significant correlation with periodontitis and the presence of Porphyromonas gingivalis in the oral cavity This bacterium could play an important role in the pathogenesis of RA through citrullination of proteins using a specific enzyme (peptidyl arginine deiminase), potentially leading to the production of anti-cyclic citrullinated peptide (anti-CCP) autoantibodies relevant to RA disease [16, 17]. It has been shown that innate-like T cells express the key Th17 transcription factor retinoic acid receptor-related orphan receptor-γt (RORγt) and that they can respond toward IL-23 by producing IL-17 and related cytokines like IL-22 [22] The importance of this finding was underscored by a mouse study, in which IL-23 overexpression (an SpA-like model using minicircle DNA technology) could induce enthesitis independent of conventional Th17 cells [26]. As disease induction did require the presence of CD4−CD8− T cells, there could be a role for IL-23 responsive innate-like T cells [27]
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