Natural killer T (NKT) cells are unconventional T cells that are activated by glycolipid antigens. They can produce a variety of inflammatory and regulatory cytokines and, therefore, modulate multiple aspects of the immune response in different pathological settings, including autoimmunity. NKT cells have also been implicated in the immunopathogenesis of autoimmune hepatitis, and in this review we summarize and analyze the main studies investigating the involvement and/or homeostasis of NKT cells in this disease. In detail, the evidence from both basic and clinical research has been specifically analyzed. Even though the experimental murine models supported a relevant role of NKT cells in immune-mediated hepatic injury, very few studies specifically investigated NKT cell homeostasis in patients with autoimmune hepatitis; however, these initial studies reported some alterations of NKT cells in these patients, which may also correlate with the disease activity to some extent. Further clinical studies are needed to investigate the potential role and use of NKT cell analysis as a disease marker of clinical relevance, and to better understand the precise cellular and molecular mechanisms by which NKT cells contribute to the pathogenesis of autoimmune hepatitis.

Background: Current evidence suggests that joint complaints can represent an extra-intestinal manifestation in patients with Celiac Disease (CD) without any rheumatic comorbidity. However, the prevalence of joint complaints in the context of both CD and rheumatic disease is not known. The aim of this study was to estimate the prevalence of joint complaints in patients with CD. Methods: We searched Medline, Embase, Cochrane, and Web of Science databases for studies reporting joint complaints in patients with CD between 1 January 1990 and 26 November 2024. Search results were screened by two independent reviewers. The pooled prevalence of joint complaints was estimated in meta-analysis using a random effects model. We conducted stratified analyses by region, age (adults vs. children), and study sample size. The Joanna Briggs Institute Critical Appraisal Tool was used to evaluate the quality of included studies, and publication bias was assessed using a funnel plot and Egger’s test. The study protocol was pre-registered in the PROSPERO database and the results were reported according to the PRISMA guidelines. Results: A total of 7414 publications were rendered in the search. Of these, 226 were reviewed in full text and 27 were included in the meta-analysis. Among 6901 patients with CD without any concomitant rheumatic diagnosis, 530 had joint complaints, yielding a weighted pooled prevalence of 10.7% (95%CI: 6.9–15.1). In meta-regression analysis, no association between the prevalence of joint complaints and patients’ clinical characteristics or demographics was found. Conclusions: This meta-analysis indicates that joint complaints in patients with CD without any specific rheumatic comorbidity are not uncommon. Increased awareness of joint complaints in CD is important to improve the diagnosis and clinical care of these patients.

Type 1 Diabetes Mellitus (T1DM) is an autoimmune disease characterized by the destruction of pancreatic β-cells. Both lymphocytes and various innate immune cells contribute to its immunopathogenesis. Among lymphocytes, in addition to CD8⁺ T cells, CD4⁺ T cells, and B cells, growing attention has been directed toward some unconventional T-cell subsets, such as TCRαβ⁺ double-negative T (DNT) cells, based on findings in several autoimmune/rheumatic diseases. This narrative review aims to summarize and analyze the available data on the potential role of DNT cells (and, in detail, the TCRαβ⁺ subset) in the immunopathogenesis of autoimmune diabetes/T1DM. Most of the current knowledge regarding DNT cell homeostasis in this pathological setting derives from experimental models, especially Non-Obese Diabetic (NOD) mice. In murine autoimmune diabetes, TCRαβ⁺DNT cells appear to exert a predominantly protective role against immune-mediated β-cell injury. These cells can be observed in multiple anatomical sites, including the thymus, peripheral blood, secondary lymphoid organs (spleen and lymph nodes) and, under pathological conditions, in non-lymphoid organs, like within the pancreas and, in detail, pancreatic islets, in the setting of autoimmune diabetes. Experimental evidence suggests that TCRαβ⁺DNT cells may attenuate the CD8⁺ T cell-mediated destruction of pancreatic β-cells, both directly and indirectly, through the inhibition of CD4⁺ T cells and B cells implicated in this immunopathological process. Unfortunately, very few studies have examined TCRαβ⁺DNT cells in patients with T1DM. This important knowledge gap highlights the need for dedicated clinical and translational research to better elucidate the role of TCRαβ⁺DNT cells in T1DM, especially given the preliminary findings pointing toward their potential immunoregulatory relevance.