The abnormal number and functional deficiency of immune cells are the pathological basis of various diseases. Recent years, the imbalance of Th17/regulatory T (Treg) cell underlies the occurrence and development of inflammation in autoimmune diseases (AID). Currently, studies have shown that material and energy metabolism is essential for maintaining cell survival and normal functions and the altered metabolic state of immune cells exists in a variety of AID. This review summarizes the biology and functions of Th17 and Treg cells in AID, with emphasis on the advances of the roles and regulatory mechanisms of energy metabolism in activation, differentiation and physiological function of Th17 and Treg cells, which will facilitate to provide targets for the treatment of immune-mediated diseases.

Background: This study aimed to search for blood biomarkers among the profiles of patients with RA-ILD by using machine learning classifiers and probe correlations between the markers and the characteristics of RA-ILD. Methods: A total of 153 RA patients were enrolled, including 75 RA-ILD and 78 RA-non-ILD. Routine laboratory data, the levels of tumor markers and autoantibodies, and clinical manifestations were recorded. Univariate analysis, least absolute shrinkage and selection operator (LASSO), random forest (RF), and partial least square (PLS) were performed, and the receiver operating characteristic (ROC) curves were plotted. Results: Univariate analysis showed that, compared to RA-non-ILD, patients with RA-ILD were older (p < 0.001), had higher white blood cell (p = 0.003) and neutrophil counts (p = 0.017), had higher erythrocyte sedimentation rate (p = 0.003) and C-reactive protein (p = 0.003), had higher levels of KL-6 (p < 0.001), D-dimer (p < 0.001), fibrinogen (p < 0.001), fibrinogen degradation products (p < 0.001), lactate dehydrogenase (p < 0.001), hydroxybutyrate dehydrogenase (p < 0.001), carbohydrate antigen (CA) 19–9 (p < 0.001), carcinoembryonic antigen (p = 0.001), and CA242 (p < 0.001), but a significantly lower albumin level (p = 0.003). The areas under the curves (AUCs) of the LASSO, RF, and PLS models attained 0.95 in terms of differentiating patients with RA-ILD from those without. When data from the univariate analysis and the top 10 indicators of the three machine learning models were combined, the most discriminatory markers were age and the KL-6, D-dimer, and CA19-9, with AUCs of 0.814 [95% confidence interval (CI) 0.731–0.880], 0.749 (95% CI 0.660–0.824), 0.749 (95% CI 0.660–0.824), and 0.727 (95% CI 0.637–0.805), respectively. When all four markers were combined, the AUC reached 0.928 (95% CI 0.865–0.968). Notably, neither the KL-6 nor the CA19-9 level correlated with disease activity in RA-ILD group. Conclusions: The levels of KL-6, D-dimer, and tumor markers greatly aided RA-ILD identification. Machine learning algorithms combined with traditional biostatistical analysis can diagnose patients with RA-ILD and identify biomarkers potentially associated with the disease.

Background. We have reported previously the insufficient absolute number or functional defects of regulatory T cells (Tregs) in patients with rheumatoid arthritis (RA), challenging conventional unspecific immunosuppressive therapy. Sirolimus, a mTOR inhibitor, is reported to allow growth of functional Tregs; here, we investigated the efficacy of low-dose sirolimus combined with conventional immunosuppressants (sirolimus immunoregulation therapy) for RA treatment with lower side effects and better tolerance. Methods. In this nonblinded and parallel-group trial, we randomly assigned 62 patients to receive conventional glucocorticoids and immunosuppressants with or without sirolimus at a dosage of 0.5 mg on alternate days for 24 weeks in a 2 : 1 ratio. The demographic features, clinical manifestations, and laboratory indicators including peripheral blood lymphocyte subgroups and CD4⁺T subsets were compared before and after the treatment. Results. Finally, 37 patients in the sirolimus group and 18 in the conventional treated group completed the 6-month study. By 24 weeks, the patients with sirolimus experienced significant reduction in disease activity indicators including DAS28, ESR, and the number of tender joints and swollen joints (p<0.001). Notably, they had a higher level of Tregs as compared with those with conventional therapy alone (p<0.05), indicating that sirolimus could partly restore the reduced Tregs. Concomitantly, their usage of immunosuppressants for controlling disease activity was decreased as compared with the conventional group with no difference in blood routine, and liver and renal functions both before and after the treatment of sirolimus and between the two groups (p>0.05). Conclusions. Low-dose sirolimus immunoregulatory therapy selectively upregulated Tregs and partly replaced the usage of immunosuppressants to control disease activity without overtreatment and evaluable side effect. Further study is required using a large sample of RA patients treated with sirolimus for a longer period. This trial is registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj=17245).

Background: Disturbed gut microbiota and associated metabolic dysfunction exist in Psoriasis. Despite the growing use of interleukin-17 inhibitor (anti-IL17) therapy, the effect of anti-IL17 on gut/skin microbiota function is not fully understood in patients with Psoriasis.Objective: Therefore, we explored whether Psoriasis is associated with alterations in selected gut/skin microbiota in a study cohort, and a longitudinal cohort study to reveal the effects of IL-17A inhibitor treatment on gut microbiota in Psoriasis.Methods: In a case-control study, 14 patients with Psoriasis and 10 age, sex and body mass index-matched Healthy Controls were recruited. Longitudinal mapping of the gut microbiome was performed using 16S rRNA gene sequencing. Mouse models were used to further study and validate the interrelationship between the skin microbiome and the gut microbiome in Psoriasis. PICRUST2 was applied to predict the function of the bacterial community.Results: In Psoriasis patients, gut microbiota dysbiosis was present with increased heterogeneity: decreased Bacteroidota and increased Firmicutes as well as Actinobacteriota predominating in Psoriasis. Escherichia-Shigella enrichment was associated with reduction in serum levels of total bile acid and markers in Apoptotic pathways. After IL-17A inhibitor treatment in Psoriasis patients, longitudinal studies observed a trend toward a normal distribution of the gut microbiome and modulation of apoptosis-related metabolic pathways. Results from a mouse model showed dysregulation of the skin microbiota in Psoriasis characterized by Staphylococcus colonization.Conclusion: The psoriatic gut/skin microbiota exhibits loss of community stability and pathogen enrichment. IL-17A inhibitors restore microbiota homeostasis and metabolic pathways, reduce pro-inflammatory cytokine expression, and alleviate symptoms in patients with Psoriasis.