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Leptin is over-secreted in many autoimmune diseases, which can promote dendritic cells (DCs) maturation and up-regulate the expression of inflammatory cytokines, but the underlying mechanisms are not fully elucidated. Considering the major role of leptin in maintaining energy balance and the significant role of glycolysis in DCs activation, our study aims to investigate whether leptin promotes the activation of DCs via glycolysis and its underlying mechanisms. We demonstrated that leptin promoted the activation of DCs, including up-regulating the expression of co-stimulatory molecules and inflammatory cytokines, enhancing the proliferation and T helper 17 (Th17) cell ratio in peripheral blood mononuclear cells (PBMC) co-cultured with leptin-stimulated DCs. Leptin also enhanced DCs glycolysis with increased glucose consumption, lactate production, and the expression of hexokinase 2 (HK2). In addition, the activation of DCs stimulated by leptin could be inhibited by the glycolysis inhibitor 2-deoxy- d -glucose (2-DG). To explore the signaling pathways involved in leptin-induced HK2 expression, we observed that the inhibitors of STAT3 (NSC74859) could repress the enhancement of HK2 triggered by leptin stimulation. Therefore, our results indicated that leptin promoted glycolytic metabolism to induce DCs activation via STAT3-HK2 pathway.

B cell dysfunction and inflammatory cytokine over‐production participate in the pathogenesis of rheumatoid arthritis (RA). Here we compared peripheral B cell homeostasis and immune functions between RA patients and healthy controls (HC) and explored vital signaling pathways involved in altered RA B cells. We found that RA patients showed significantly decreased frequencies of peripheral CD19(+)CD27(+)CD24(high) regulatory B (Breg) cells but increased frequencies of CD19(+)CD27(+)CD38(high) plasmablasts and CD19(+)CD138(+) plasma cells, and higher levels of serum immunoglobulin (Ig)M and IgG. Compared to HC peripheral B cells, RA peripheral B cells had more increased proliferation and higher expression of activation markers. Importantly, our results showed that RA peripheral B cells displayed the mTOR signaling pathway to be more activated, and inhibition of mTOR could restore RA B cell homeostasis and functions. RA serum‐treated B cells exhibited more increased expressions of mTOR, which could be restored with the addition of anti‐interleukin (IL)‐27 neutralizing antibody. Serum IL‐27 levels were significantly increased in RA patients and positively correlated with disease activity, the frequencies of plasma cells and the levels of autoantibodies. In vitro, IL‐27 notably promoted immune dysfunction of RA B cells, which were inhibited by anti‐IL‐27 neutralizing antibody. Also, the mTOR pathway was more activated in IL‐27‐treated RA B cells, and mTOR inhibition apparently reversed abnormalities of RA B cells mediated by IL‐27. These results suggest that increased serum IL‐27 levels could promote peripheral B cell dysfunction in RA patients via activating the mTOR signaling pathway. Thus, IL‐27 may play a pro‐pathogenic role in the development of RA, and antagonizing IL‐27 could be a novel therapy strategy for RA.

Huaier, a traditional Chinese medicine, is currently used to treat certain types of cancer in the clinic and is also regarded as an immune-modulating and immune-enhancing agent that regulates immune cells. Emerging evidence indicates that an imbalance of immune cells, such as CD4+ T helper (Th) lymphocytes, contributes to the progression of immune thrombocytopenia (ITP), but the effects of Huaier on the regulation of CD4+ T cells are not yet fully elucidated. In the present study, Jurkat cells and peripheral blood mononuclear cells (PBMCs) from patients with ITP and healthy volunteers were treated with Huaier aqueous extract (HR). The CCK-8 assay revealed that HR suppressed the proliferation of Jurkat cells in a dose-dependent manner, whereas 3 mg/mL could decrease cell viability by 50%. At the latter concentration, the activation of CD4+ T cells from patients with ITP was partially attenuated. In addition, HR could correct the unbalanced Th1/Th2 polarization and inhibit the secretion of pro-inflammatory factors interleukin (IL)-2, tumor necrosis factor-α, and interferon-γ. It also suppressed Treg and facilitated Th17 differentiation, but did not change the levels of IL-10 and transforming growth factor-β. Thus, this study provides more information on how Huaier regulates cellular immunity and improves our understanding of the use of Huaier in ITP.

Iguratimod (IGU) is a novel disease modified anti-rheumatic drug, which has been found to act directly on B cells for inhibiting the production of antibodies in rheumatoid arthritis (RA) patients. Follicular helper T (Tfh) cells, a key T cell subsets in supporting B cell differentiation and antibody production, have been shown to play critical roles in RA. However, whether IGU can inhibit RA Tfh cells which further restrains B cell function remains unclear. Here, we aimed to explore the roles of IGU in regulating RA circulating Tfh (cTfh) cell function and investigate the potential mechanism associated with cell glucose metabolism. In our study, we found that IGU could act on RA-CD4

Background: Systemic lupus erythematosus(SLE) is characterized by loss of immune tolerance and imbalance of immune cell subsets. NK cells contribute to regulate both the innate and adaptive immune response. In this study, we aimed to detect peripheral NK cell subsets in SLE patients, investigate their cytotoxic effect on activated CD4+ T cells, and explore intrinsic mechanisms contributing to NK cell abnormality.Methods: Blood samples from healthy controls(HCs) and patients with SLE and rheumatoid arthritis(RA) were collected. The NK count, NK subsets(CD56bright , CD56dimCD57- , and CD56dimCD57+), phenotypes, along with apoptosis were analysed by flow cytometry. The t-stochastic neighbor embedding (tSNE) analysis of lymphocytes based on immune cells flow cytometry markers was performed. Mitochondrial reactive oxygen species(mtROS) and total ROS levels in NK cells were detected by MitoSOX Red and DCFH-DA staining respectively. Published data(GSE63829 and GSE23695) from Gene Expression Omnibus(GEO) was analyzed by Gene Set Enrichment Analysis(GSEA).Results: NK count was down-regulated in untreated SLE patients in comparison to untreated RA patients or HCs and the count was negatively correlated with disease activity. SLE patients exhibited a selective reduction in CD56dimCD57+ NK cell proportion, which was negatively correlated with Systemic Lupus Erythematosus Disease Activity Index(SLEDAI) and positively correlated with complement C3 and C4. CD56dimCD57+NK cells exhibited increased cytotoxic effect on activated CD4+ T cells relative to CD56dimCD57- NK cells. Compared with HCs, CD56dimCD57+ NK cells in SLE patients exhibited impaired cytotoxic function, increased apoptosis and higher levels of both mtROS and ROS. GSEA analysis indicated that ROS pathway was significantly enriched in NK cells from lupus. Compared with CD56dimCD57- NK cells in SLE patients, CD56dimCD57+ NK cells showed higher levels of oxidative stress and apoptosis. Furthermore, oxidative stress levels were negatively correlated with perforin expression and positively correlated with apoptosis. CD56dimCD57+ NK cells were more prone to undergo apoptosis when exposed to ROS in vitro. Conclusion: Beyond the reduced NK cell number, our study demonstrated a selective loss of mature CD56dimCD57+ NK cell subset, which was conversely correlated with disease activity. This subset showed attenuated cytotoxic function, up-regulated endogenous apoptosis and increased oxidative stress, which might contribute to NK cell abnormality.

Systemic lupus erythematosus (SLE) is characterized by loss of immune tolerance and imbalance of immune cell subsets. Natural killer (NK) cells contribute to regulate both the innate and adaptive immune response. In this study, we aimed to detect alterations of peripheral NK cells and explore intrinsic mechanisms involving in NK cell abnormality in SLE.Blood samples from healthy controls (HCs) and patients with SLE and rheumatoid arthritis (RA) were collected. The NK count, NK subsets (CD56Total peripheral NK count was down-regulated in untreated SLE patients in comparison to that in untreated RA patients and HCs. SLE patients exhibited a selective reduction in peripheral CD56Our study demonstrated a selective loss of mature CD56

Leptin is over-secreted in many autoimmune diseases, which can promote dendritic cells (DCs) maturation and up-regulate the expression of inflammatory cytokines, but the underlying mechanisms are not fully elucidated. Considering the major role of leptin in maintaining energy balance and the significant role of glycolysis in DCs activation, our study aims to investigate whether leptin promotes the activation of DCs via glycolysis and its underlying mechanisms. We demonstrated that leptin promoted the activation of DCs, including up-regulating the expression of co-stimulatory molecules and inflammatory cytokines, enhancing the proliferation and T helper 17 (Th17) cell ratio in peripheral blood mononuclear cells (PBMC) co-cultured with leptin-stimulated DCs. Leptin also enhanced DCs glycolysis with increased glucose consumption, lactate production, and the expression of hexokinase 2 (HK2). In addition, the activation of DCs stimulated by leptin could be inhibited by the glycolysis inhibitor 2-DG. To explore the signaling pathways involved in leptin-induced HK2 expression, we observed that only the inhibitors of STAT3 (NSC74859) could repress the enhancement of HK2 triggered by leptin stimulation. Therefore, our results indicated that leptin promoted glycolytic metabolism to induce DCs activation via STAT3-HK2 pathway.

Background When the minority college students from the ethnic minority communities come to study in Chinese Han region, they encounter adapting difficulties of culture and socio-psychology, in which empathy plays a crucial role. Current instruments used to measure empathy have many limited effectiveness. The empathy quotient (EQ) scale which has been validated in many countries was explicitly designed for clinical applications and was intended to be sensitive to a lack of empathy. This study is to develop a complete Chinese version of the EQ scale and to assess its reliability and validity among Chinese minority college students in the Han Chinese region. Methods A total of 1638 Chinese minority college students in the Han region were selected and were randomly divided into two groups. One group of 818 students took part in the implementation of the exploratory factor analysis while the other group of 820 students participated in the confirmatory factor analysis. Results Twenty-nine items of the EQ were retained based on the factor analysis and four factors were extracted: self-awareness, cognitive empathy, social skills, and emotional reactivity, which can explain 51.793% of the total variance. The factors of the EQ scale were significantly correlated with each other, with the correlation coefficient ranging from 0.316 to 0.563. The coefficient of internal consistency (Cronbach’s α) was 0.824 for the total scale and ranged from 0.640 to 0.818 for the subscales. Confirmatory factor analysis proved that the measured data fitted well with the hypothesized four-factor model. All of the items in the scale fitted the model well, and the point-measure correlation coefficient had acceptable consistency. Conclusions The refined 29-item Chinese version of the EQ possesses good reliability and validity, and can be applied in assessing empathy among Chinese minority college students.