UNASSIGNED: Vitiligo is an immune-related skin disease. Cytokines regulate immune response and inflammation and are involved in the pathogenesis of vitiligo.
UNASSIGNED: To assess the serum levels of pro-inflammatory cytokines pre- and post- systemic glucocorticoid treatment in patients with active vitiligo.
UNASSIGNED: We measured serum cytokine levels using the enzyme-linked immunosorbent assay in 31 patients with active vitiligo before and after treatment. All patients received systemic glucocorticoid (compound betamethasone injection) in combination with topical halometasone cream and tacrolimus ointment for 3 months. Twenty healthy controls were also examined. The cytokines measured included TNF-α, IL-1β, IL-6, IFN-γ, IL-2, IL-17, IL-10, IL-8, and CXCL10.
UNASSIGNED: The serum levels of TNF-α, IL-1β, IL-6, IFN-γ, IL-2, IL-17, IL-8, and CXCL10 were significantly higher, and levels of IL-10 were lower in vitiligo patients compared to controls. Additionally, serum IFN-γ (r = 0.378; p = 0.036), IL-17 (r = 0.426; p = 0.017), and CXCL10 (r = 0.514; p = 0.003) showed a positive correlation with affected body surface area in vitiligo patients. After 3 months of systemic glucocorticoid treatment, the levels of IL-1β, IFN-γ, IL-2, IL-17, and CXCL10 in responders were significantly decreased and nearly restored to normal levels. The IL-10 level was also increased in response to treatment. In contrast, the non-responder group had persistently high IL-6, IL-17, IL-8, and CXCL10 levels, and negligible changes in TNF-α, IL-1β, IFN-γ, IL-2, and IL-10.
UNASSIGNED: Our study indicated that the levels of inflammatory cytokines were significantly ameliorated in the glucocorticoid responder group. Altered cell-mediated immunity may contribute to the resistance in vitiligo. The cytokines such as TNF-α, IL-1β, IFN-γ and IL-2 could serve as therapeutic targets for managing glucocorticoid-resistant vitiligo.

Resatorvid (TAK-242), a specific inhibitor of Toll-like receptor-4 (TLR4), has attracted attention for its anti-inflammatory properties. Despite this, few studies have evaluated its effects on ulcerative colitis (UC). This study aimed to investigate the effects of TAK-242 on macrophage polarization and T helper cell balance and the mechanism by which it alleviates UC. Our findings indicated that TLR4 expression was elevated in patients with UC, a mouse model of UC, and HT29 cells undergoing an inflammatory response. TAK‑242 treatment reduced apoptosis in TNF-α and LPS-stimulated HT29 cells and alleviated symptoms of dextran sulfate sodium (DSS)‑induced colitis in vivo. TAK‑242 downregulated TLR4 expression and decreased the secretion of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β while enhancing IL-10 production. TAK-242 also reduced M1 macrophage polarization and diminished Th1 and Th17 cell infiltration while increasing Th2 cell infiltration and M2 macrophage polarization both in vitro and in vivo. Mechanistically, TAK-242 inhibited the JAK2/STAT3 signaling pathway, an important regulator of macrophage polarization and T helper cell balance. Furthermore, the in vivo and in vitro effects of TAK-242 were partially negated by the administration of the JAK2/STAT3 antagonist AG490, suggesting that TAK-242 inhibits the JAK2/STAT3 pathway to exert its biological activities. Taken together, this study underscores TAK-242 as a promising anti-UC agent, functioning by modulating macrophage polarization and T helper cell balance via the TLR4/JAK2/STAT3 signaling pathway.

UNASSIGNED: Immune dysregulation plays a key role in acute myeloid leukemia (AML). We aimed to explore the correlation between T helper cell 17 (Th17) and the regulatory cells (Tregs) in the peripheral blood of patients with newly diagnosed (ND) AML and bone marrow blast cells, as well as minimal residual disease (MRD) before and after treatment.
UNASSIGNED: Changes in Th17 and Treg cells in the peripheral blood of 32 patients with ND AML were observed before and after induction chemotherapy with cytarabine for seven days and anthracycline for three days. The levels of inflammatory cytokines were measured using an enzyme-linked immunosorbent assay. Correlation analysis between bone marrow blast cells and Th17 and Treg cell frequencies was performed using the Pearson\'s correlation test. Frequencies of Th17 and Treg cells and MRD were assessed using flow cytometry.
UNASSIGNED: IL-6, IL-10, IL-17A, and GM-CSF levels gradually increased in patients with ND AML and CR and NR patients. The percentages of Th17 and Treg cells positively correlated with those of blast cells. In addition, the frequencies of Th17 and Treg cells in MRD-positive patients were higher than those in MRD-negative patients at the initial induction and after three months of chemotherapy. The frequencies of Tregs and Th17 cells positively correlated with MRD onset.
UNASSIGNED: Increased Th17 and Treg cell levels were positively correlated with onset of AML, poor remission, and MRD.

OBJECTIVE: To observe the effect of electroacupuncture (EA) of scalp acupoint (Dingnieqian-xiexian, MS6) on expression of retinoid-related orphan receptor γT (ROR γ t), interleukin (IL)-17A, IL-10, transfor-ming growth factor-β1 (TGF-β1), IL-6, IL-21, and IL-17A+ Thelper cells(Th) 17 and forkhead transcription factor P3 (FOXP3)+ regulatory T cells (Treg) differentiation of ischemic cortex in ischemic stroke rats, so as to explore its molecular mechanisms underlying relief of inflammatory injury of ischemic stroke.
METHODS: A total of 120 male SD rats were randomly assigned to sham operation, model, EA, inhibitor, agonist and EA+agonist groups, with 15 rats in each group. The ischemic stroke model was established by occlusion of the left middle cerebral artery according to Longa\'s methods. For rats of the EA group and EA+agonist group, EA (2 Hz/100 Hz, 1 mA) was applied to bilateral MS6 for 30 min, once daily for 7 days. Rats of the inhibitor group received intraperitoneal injection of solution of SR1001 (RORγt inhibitor) (2.5 mg/mL, 10 mg/kg), once daily for 7 days. Rats of the agonist and EA+agonist groups received intraperitoneal injection of solution of SR1078 (RORγt agonist) (5 mg/mL, 5 mg/kg) before EA, once daily for 7 days. Rats of the sham operation and model groups were grabbed and fixed in the same way with the other groups. The Zea-longa\'s score, modified neurological severity score (mNSS) and the neurobehavioral score were assessed before and after the intervention. At the end of experiments, the ischemic cortex tissue was collected. The 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining was used to detect the volume of cerebral infarction. The expression of RORγt mRNA was detected by real-time quantitative PCR；the protein expression levels of RORγt, IL-17A, IL-10 and TGF-β1 were detected by Western blot；the immunoactivity of IL-6 and IL-21 were detected by immunohistochemistry；the fluorescence areas of IL-17A+Th17 and FOXP3+Treg cells were measured by immunofluorescence and their ratio was calculated in the tissue of ischemic cortex.
RESULTS: Relevant to the sham operation group, the model group had a significant increase in the Zea-Longa\'s score, mNSS score, neurobehavioral score, cerebral infarct volume, expression levels of RORγt mRNA and protein, IL-17A protein, IL-6 and IL-21 immunoactivity, IL-17A+Th17 immunofluorescence intensity, and the ratio of IL-17A+Th17/FOXP3+Treg (P<0.01), and an obvious decrease in the expression levels of TGF-β1 and IL-10 proteins and FOXP3+Treg immunofluorescence intensity (P<0.01). In contrast to the model group, both EA and inhibitor groups had a significant decrease in the Zea-Longa\'s score, mNSS score, neurobehavioral score, cerebral infarct volume, expression levels of RORγt mRNA and protein, IL-17A protein, IL-6 and IL-21 immunoactivity, IL-17A+Th17 immunofluorescence intensity, and the ratio of IL-17A+Th17/FOXP3+Treg (P<0.01, P<0.05), and a marked increase in the expression levels of TGF-β1 and IL-10 proteins and FOXP3+Treg immunofluorescence intensity (P<0.05, P<0.01), while the above indicators of the agonist group were all reversed (P<0.01, P<0.05). Comparison between the agonist and EA+agonist groups showed that the Zea-Longa\'s score, mNSS score, neurobehavioral score, cerebral infarct volume, expression levels of RORγt mRNA and protein, IL-17A protein, IL-6 and IL-21 immunoactivity, IL-17A+Th17 immunofluorescence intensity, and the ratio of IL-17A+Th17/FOXP3+Treg were significantly lower (P<0.01, P<0.05), and the expression of TGF-β1 and IL-10 proteins and FOXP3+Treg immunofluorescence intensity were obviously higher (P<0.01, P<0.05) in the EA+agonist group than in the agonist group, suggesting that EA intervention can effectively weaken the effects of RORγt agonist.
CONCLUSIONS: EA of scalp acupoint MS6 can effectively improve the neurological function, behavior reaction and reduce cerebral infarct volume in ischemic stroke rats, which may be associated with its functions in down-regulating the expression of RORγt and promoting the balance of IL-17A+Th17/FOXP3+Treg to alleviate inflammatory injury after ischemic stroke.
目的: 观察电头针干预对局灶性脑缺血大鼠缺血皮层区维甲酸相关孤儿受体γt（RORγt）、辅助性T细胞（Th）17和调节性T细胞（Treg）的影响，从调控免疫细胞平衡的角度探讨电头针缓解缺血性脑卒中炎性损伤的分子机制。方法: SD大鼠随机分为假手术组、模型组、电头针组、抑制剂组、激动剂组、电头针+激动剂组，每组15只。采用线栓法复制大脑中动脉栓塞大鼠模型。电头针组取双侧顶颞前斜线电针干预，每次30 min；抑制剂组给予RORγt抑制剂SR1001溶液腹腔注射；激动剂组给予RORγt激动剂SR1078溶液腹腔注射；电头针+激动剂组在腹腔注射SR1078溶液基础上再行电头针干预；所有干预均1次/d，连续7 d。干预前、后对各组大鼠行Zea-Longa评分，神经功能缺损量表（mNSS）评分和神经行为学评分。TTC染色法检测脑梗死体积；实时荧光定量PCR法检测脑缺血区皮层中RORγt mRNA的表达水平；Western blot法检测脑缺血区皮层中RORγt、白细胞介素（IL）-17A、IL-10和转化生长因子β1（TGF-β1）的蛋白表达水平；免疫组织化学法检测脑组织中IL-6、IL-21的阳性表达；免疫荧光染色法检测脑缺血区皮层中IL-17A+Th17和叉头状转录因子P3（FOXP3）+Treg细胞的阳性表达面积并计算其比值。结果: 与假手术组比较，模型组Zea-Longa评分、mNSS评分与神经行为学评分升高（P<0.01），脑梗死体积增大（P<0.01），缺血区皮层RORγt mRNA及蛋白、IL-17A蛋白表达水平升高（P<0.01），IL-10、TGF-β1蛋白表达水平降低（P<0.01），IL-6、IL-21阳性表达升高（P<0.01），IL-17A+Th17/FOXP3+Treg阳性表达面积比值升高（P<0.01）。与模型组比较，电头针组和抑制剂组Zea-Longa评分、mNSS评分与神经行为学评分降低（P<0.01），脑梗死体积显著缩小（P<0.01），RORγt mRNA及蛋白、IL-17A蛋白表达水平降低（P<0.01，P<0.05），IL-10、TGF-β1蛋白表达水平升高（P<0.05，P<0.01），IL-6、IL-21阳性表达降低（P<0.01），IL-17A+Th17/FOXP3+Treg阳性表达面积比值降低（P<0.01）；而激动剂组以上指标的结果均呈相反趋势（P<0.01，P<0.05）。与激动剂组比较，电头针+激动剂组Zea-Longa评分、mNSS评分与神经行为学评分降低（P<0.01），脑梗死体积显著缩小（P<0.05），RORγt mRNA及蛋白、IL-17A蛋白表达水平降低（P<0.01，P<0.05），IL-10、TGF-β1蛋白表达水平升高（P<0.01，P<0.05），IL-6、IL-21阳性表达降低（P<0.05，P<0.01），IL-17A+Th17/FOXP3+Treg阳性表达面积比值降低（P<0.01）。结论: 下调RORγt的表达，促进IL-17A+Th17/FOXP3+ Treg比例恢复平衡可能是电头针缓解缺血性脑卒中炎性神经损伤的机制之一。.

BACKGROUND: Heat shock protein A4 (HSPA4) belongs to molecular chaperone protein family which plays important roles within variable cellular activities, including cancer initiation and progression. However, the prognostic and immunological significance of HSPA4 in lung adenocarcinoma (LUAD) has not been revealed yet.
OBJECTIVE: To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.
METHODS: We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database. The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test. Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors, including HSPA4, in LUAD. Gene set enrichment analysis (GSEA) was conducted to identify the key signaling pathways associated with HSPA4. The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis (ssGSEA).
RESULTS: Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage, advanced pathologic stage, progression disease status of primary therapy outcome and female subgroups with LUAD. In addition, increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival. GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response, particularly through diminishing the function of cytotoxicity cells and CD8 T cells. The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells, while a negative correlation was observed with cytotoxic cell infiltration levels.
CONCLUSIONS: Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.

Innate lymphoid cells (ILCs), as the innate counterpart of CD4+ T helper (Th) cells, play crucial roles in maintaining tissue homeostasis. While the ILC subsets and their corresponding Th subsets demonstrate significant similarities in core programming related to effector function and regulatory mechanisms, their principal distinctions, given their innate and adaptive lymphocyte nature, remain largely unknown. In this study, we have employed an integrative analysis of 294 bulk RNA-sequencing results across all ILC and Th subsets, using scRNA-seq algorithms. Consequently, we identify two genesets that predominantly differentiate ILCs from Th cells, as well as three genesets that distinguish various immune responses. Furthermore, through chromatin accessibility analysis, we find that the ILC geneset tends to rely on specific transcriptional regulation at promoter regions compared with the Th geneset. Additionally, we observe that ILCs and Th cells are under differential transcriptional regulation. For example, ILCs are under stronger regulation by multiple transcription factors, including RORα, GATA3, and NF-κB. Otherwise, Th cells are under stronger regulation by AP-1. Thus, our findings suggest that, despite the acknowledged similarities in effector functions between ILC subsets and corresponding Th subsets, the underlying regulatory machineries still exhibit substantial distinctions. These insights provide a comprehensive understanding of the unique roles played by each cell type during immune responses.

UNASSIGNED: The role of granulocyte-macrophage-colony-stimulating factor-producing T helper (ThGM) cells in colorectal cancer (CRC) development remains unclear. This study characterizes the function of ThGM cells in mouse CRC.
UNASSIGNED: Mouse CRC was induced by administrating azoxymethane and dextran sulfate sodium. The presence of ThGM cells in CRC tissues and the mechanistic target of rapamycin complex 1 (mTORC1) signaling in ThGM cells was detected by flow cytometry. The impact of mTORC1 signaling on ThGM cell function was determined by in vitro culture. The effect of ThGM cells on CRC development was evaluated by adoptive transfer assays.
UNASSIGNED: ThGM cells, which expressed granulocyte-macrophage-colony-stimulating factor (GM-CSF), accumulated in CRC tissues. mTORC1 signaling is activated in CRC ThGM cells. mTORC1 inhibition by rapamycin suppressed ThGM cell differentiation and proliferation and resulted in the death of differentiating ThGM cells. mTORC1 inhibition in already differentiated ThGM cells did not induce significant cell death but decreased the expression of GM-CSF, interleukin-2, and tumor necrosis factor-alpha while impeding cell proliferation. Furthermore, mTORC1 inhibition diminished the effect of ThGM cells on driving macrophage polarization toward the M1 type, as evidenced by lower expression of pro-inflammatory cytokines, major histocompatibility complex class II molecule, and CD80 in macrophages after co-culture with rapamycin-treated ThGM cells. Lentivirus-mediated knockdown/overexpression of regulatory-associated protein of mTOR (Raptor) confirmed the essential role of mTORC1 in ThGM cell differentiation and function. Adoptively transferred ThGM cells suppressed CRC growth whereas mTORC1 inhibition abolished this effect.
UNASSIGNED: mTORC1 is essential for the anti-CRC activity of ThGM cells.

With the improved quality of life, oral health is under increased pressure. Numerous common oral mucosal diseases, such as oral lichen planus(OLP) and gingivitis, are related to the destruction of the oral immune barrier. The cytokines secreted by T-helper 17 (Th17) cells are essential for maintaining oral immune homeostasis and play essential roles in immune surveillance. When antigens stimulate the epithelium, Th17 cells expand, differentiate, and generate inflammatory factors to recruit other lymphocytes, such as neutrophils, to clear the infection, which helps to maintain the integrity of the epithelial barrier. In contrast, excessive Th17/IL-17 axis reactions may cause autoimmune damage. Therefore, an in-depth understanding of the role of Th17 cells in oral mucosa may provide prospects for treating oral mucosal diseases. We reviewed the role of Th17 cells in various oral and skin mucosal systemic diseases with oral characteristics, and based on the findings of these reports, we emphasize that Th17 cellular response may be a critical factor in inflammatory diseases of the oral mucosa. In addition, we should pay attention to the role and relationship of \"pathogenic Th17\" and \"non-pathogenic Th17\" in oral mucosal diseases. We hope to provide a reference for Th17 cells as a potential therapeutic target for treating oral mucosal inflammatory disorders in the future.

Autoreactive CD4+ helper T cells are implicated in the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD). Both PD-1+CXCR5+CD4+ T follicular helper (Tfh) cells and PD-1+CXCR5-CD4+ T peripheral helper (Tph) cells can contribute to B-cell immune responses and the production of antibodies. Here we show the effect of B-cell depletion with rituximab on the homeostasis of Tfh cells, Tph cells and their subsets in patients with NMOSD. After rituximab treatment, total Tph cells, total Tfh cells, Tph17 cells, Tph17.1 cells, Tph1 cells, and Tfh1 cells tended to decrease at month 1, but gradually increased at month 6 and restored at month 12. Besides, Tph17.1 cells and Tfh17.1 cells were correlated with the proportion of CD19- antibody-secreting cells. Our data suggest that rituximab induced a fluctuation of proinflammatory Tph and Tfh subsets within one year after initiation of the treatment.

Systemic lupus erythematosus (SLE), an autoimmune disease affecting multiple organs and tissues, is often complicated by musculoskeletal diseases. T helper cells (Th) play an important role in mediating lupus. With the rise of osteoimmunology, more studies have shown shared molecules and interactions between the immune system and bones. Th cells are vital in the regulation of bone metabolism by directly or indirectly regulating bone health by secreting various cytokines. Therefore, by describing the regulation of Th cells (including Th1, Th2, Th9, Th17, Th22, regulatory T cells (Treg), and follicular T helper cells (Tfh) in bone metabolism in SLE, this paper offers certain theoretical support for abnormal bone metabolism in SLE and provides new prospects for future drug development.