Percentage Of Th17 Cells Research Articles

Nebulized Mycobacterium vaccae protects against asthma by attenuating the imbalance of IRF4/IRF8 expression in dendritic cells

Objective: To assess the effects of nebulized inhaled Mycobacterium vaccae on allergic airway inflammation, airway hyperresponsiveness, and Th1/Th2 cell imbalance in mice with ovalbumin (OVA)-induced asthma. Methods: Mice received OVA sensitization and challenge for establishment of the asthmatic model. For intervention, mice received Mycobacterium vaccae nebulization once every other day from the first day of sensitization to the day before challenge. After challenge, pulmonary histological analysis and airway responsiveness measurement were performed. In addition, Th1/Th2 cytokines and OVA-specific IgE levels in bronchoalveolar lavage fluid were measured by ELISA. Th1/Th2 subset ratios and the expression of interferon-regulatory factor 4 (IRF4), IRF8 and Toll-like receptor 4 (TLR4) in dendritic cells were evaluated by flow cytometry. Results: Severe inflammatory infiltration and airway hyperresponsiveness were observed in OVA-induced asthmatic mice. Asthmatic mice showed higher Th2 cytokine concentration and increased percentage of Th2 cells, along with lower Th1 cytokine concentration and reduced percentage of Th1 cells compared with the normal control. Moreover, an imbalance of IRF4+ and IRF8+ in dendritic cells was found in asthmatic mice. Nebulized inhaled Mycobacterium vaccae reduced airway hyperresponsiveness and inflammation in OVA-induced asthmatic mice. In addition, nebulized inhaled Mycobacterium vaccae enhanced TLR4 and IRF8 expression, and alleviated the imbalance of Th1/Th2 as well as IRF4+ and IRF8+ in dendritic cells. Conclusions: Nebulized inhaled Mycobacterium vaccae protects against asthma by alleviating the imbalance of Th1/Th2 and IRF4/ IRF8 in OVA-induced asthmatic mice.

Increase in different peripheral effector T subsets in acute and chronic gout

ObjectivesGout (GT) belongs to a group of diseases caused by a purine metabolic disorder. GT is an inflammatory disease caused by the local deposition of uric acid in joints or adjacent tissues. The mechanism of GT is not fully explained, especially the involvement of an immune system. The objective of this study was to investigate the change in peripheral CD4+T subsets in acute and chronic GT patients. MethodsA total of 205 patients with acute and chronic GT and 87 healthy controls (HCs) were enrolled. The medical history improvement, clinical indicators, immune function, and peripheral CD4+T-lymphocyte detected by modified flow cytometry were collected in all subjects. ResultsCompared with healthy controls, acute and chronic GT patients remarkably increased the absolute counts of T helper type 1 (Th1) cells (P < 0.05) and decreased the absolute number of Treg cells without significant difference (P > 0.05). In addition, the absolute number and percentage of Th1 cells and Th1/T helper type 2 (Th2) ratio increased significantly, and the ratio of Th2 cells decreased in patients with chronic GT compared to patients with acute GT (P < 0.05). The results of Spearman correlation analysis showed a notably negative correlation between the level of CRP and the absolute counts of peripheral Th1 and Th17 cells in patients with GT, while the levels of CD4+T sunsets had no significant correlation with ESR and uric acid. The course of the disease, the absolute number of Th1 cells, the percentage of Th1 cells and the ratio of Th1/Th2 cells were significantly associated with the progression of the disease, and the course of the disease was an independent risk factor for patients with chronic GT. ConclusionThe balance of Th1 and Th2 were involved throughout the whole stages of GT, Th17 cells then become involved in the disease process as the disease progresses.

Stanniocalcin‐1 attenuates collagen‐induced arthritis through inhibiting STAT3 phosphorylation and Th17 response

AbstractRheumatoid arthritis (RA) is an autoimmune disease, associated with chronic inflammation and the imbalance of Th17/Treg. Stanniocalcin‐1 (STC‐1), a glycoprotein, was found to have anti‐inflammatory, anti‐oxidative stress and anti‐apoptosis properties. The present study aimed to investigate the immunomodulatory effect of STC‐1 and its potential value in the treatment of RA. Here, a mouse model of collagen‐induced arthritis (CIA) was established. Then body weight, joint erythema and swelling were measured in CIA mice with or without STC‐1 treatment. Haematoxylin and eosin (H and E) staining was performed to determine histopathological change. Moreover, the percentage of Th17 and Treg cells in the spleen and inguinal lymph nodes (ILNs) and the culture supernatant in polarizing conditions were examined by flow cytometry. Cytokines in serum were detected by ELISA. As a result, the arthritis score, histologic inflammation and cartilage destruction were decreased in CIA mice treated with STC‐1. STC‐1 increased the level of transforming growth factor‐β and inhibited the expression of interleukin‐17. In CIA mice, the percentage of CD4+IL‐17A+ cells in the spleen and ILNs were decreased after STC‐1 treatment, while the level of CD4+Foxp3+ cells did not change significantly. In vitro, STC‐1 inhibited Th17 cell differentiation and STAT3 phosphorylation in CD4+ T cells under Th17 cell‐polarizing conditions. Collectively, the results demonstrated that STC‐1 alleviated RA by inhibiting Th17 cell differentiation through regulating STAT3 phosphorylation. STC‐1 may be a potential drug for the treatment of RA.

α-Synuclein induces Th17 differentiation and impairs the function and stability of Tregs by promoting RORC transcription in Parkinson's disease

BackgroundParkinson’s disease (PD) is characterized by the loss of dopaminergic neurons (DA) and the accumulation of Lewy body deposits composed of alpha-Synuclein (α-Syn), which act as antigenic epitopes to drive cytotoxic T-cell responses in PD. Increased T helper 17 (Th17) cells and dysfunctional regulatory T cells (Tregs) have been reported to be associated with the loss of DA in PD. However, the mechanism underlying the Th17/Treg imbalance remains unknown. MethodsHere, we examined the percentage of Th17 cells, the percentage of Tregs and the α-Syn level and analysed their correlations in the peripheral blood of PD patients and in the substantia nigra pars compacta (SNpc) and spleen of MPTP-treated mice and A53 transgenic mice. We assessed the effect of α-Syn on the stability and function of Tregs and the differentiation of Th17 cells and evaluated the role of retinoid-related orphan nuclear receptor (RORγt) upregulation in α-Syn stimulation in vivo and in vitro. ResultsWe found that the α-Syn level and severity of motor symptoms were positively correlated with the increase in Th17 cells and decrease in Tregs in PD patients. Moreover, α-Syn stimulation led to the loss of Forkhead box protein P3 (FOXP3) expression in Tregs, accompanied by the acquisition of IL-17A expression. Increased Th17 differentiation was detected upon α-Syn stimulation when naïve CD4+ T cells were cultured under Th17-polarizing conditions. Mechanistically, α-Syn promotes the transcription of RORC, encoding RORγt, in Tregs and Th17 cells, leading to increased Th17 differentiation and loss of Treg function. Intriguingly, the increase in Th17 cells, decrease in Tregs and apoptosis of DA were suppressed by a RORγt inhibitor (GSK805) in MPTP-treated mice. ConclusionTogether, our data suggest that α-Syn promotes the transcription of RORC in circulating CD4+ T cells, including Tregs and Th17 cells, to impair the stability of Tregs and promote the differentiation of Th17 cells in PD. Inhibition of RORγt attenuated the apoptosis of DA and alleviated the increase in Th17 cells and decrease in Tregs in PD.

MAKING A STAT DIAGNOSIS IN A PATIENT PRESENTING WITH VILLOUS ATROPHY

<h3>Introduction</h3> Signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) gene mutations are highly penetrant, resulting in enhanced STAT1-dependent responses to interferon-alpha/beta and interferon-gamma signaling, and impaired Th17 development. This manifests as recurrent infections, cytopenias, and autoimmune disease. Herein, we present a case of a child diagnosed with a STAT1 mutation. <h3>Case Description</h3> A 3-year-old female presented for secondary evaluation of persistent gastrointestinal and respiratory symptoms, recurrent sinopulmonary and skin infections, failure to thrive, and developmental delay. An esophagogastroduodenoscopy performed elsewhere showed increased duodenal intraepithelial lymphocytes with crypt hyperplasia and villous atrophy. Testing for Celiac disease and autoimmune enteritis were negative. Chest computed tomography showed bilateral bronchiectasis with mucous plugging. Bronchoalveolar lavage culture was positive for Streptococcus pneumoniae. Laboratory workup was notable for anemia and T-cell lymphopenia. Quantitative lymphocytes showed a low CD3+ count of 446 cells/mcL, low CD4+ count of 185 cells/mcL, and low CD8+ count of 194 cells/mcL. Lymphocyte proliferation to antigens showed essentially absent total CD45+ lymphocytes and CD3+ T cell responses to Candida and Tetanus toxoid antigens. Genetic testing later revealed a heterozygous, pathogenic c.1154C>T (p.Thr385Met) variant in the STAT1 gene. Additional testing for Th17 enumeration showed a decreased IL17 and Th17 cell percentage. She was treated with supportive care, antibiotics, and referred to Medical Genetics for additional education and counseling. <h3>Discussion</h3> STAT1-GOF gene mutations are rare and associated with variable phenotypes and disease severity. Genetic testing can help determine the cause of complex, multisystem diseases. Stem cell transplant, immunoglobulin replacement therapy, and JAK inhibitors are potential treatment considerations.

Insulin-binding protein-5 down-regulates the balance of Th17/Treg

The inflammatory response plays critical important role in tissue hemostasis. Our previous study showed insulin-binding protein-5 (IGFBP5) could enhance the regeneration of tissue defect under inflammation condition, but the function of IGFBP5 in controlling inflammation and regulating immune responses remains unclear. In present study, we studied the regulatory effect of IGFBP5 on T cell immune response in vitro, and the maintenance of Th17/Treg balance in vivo by using dextran sulfate sodium salt (DSS)-induced colitis in mice. The results showed that IGFBP5 inhibited the differentiation of CD4+ T cells into Th17 subset while promoted its differentiation into Treg subsets. Further results of animal experiments demonstrated that recombinant IGFBP5 reversed the imbalance of Th17/Treg and alleviated the severity of DSS-induced colitis. The percentage of Th17 cells decreased and the percentage of Treg cells increased in the inflamed colon tissue and mesenteric lymph nodes of mice with colitis after IGFBP5 treatment. Besides, pro-inflammatory cytokines such as TNF-α, IL-1β and IFN-γ in serum were suppressed after the treatment of IGFBP5. Moreover, the function of IGFBP5 in regulating Th17/Treg balance could be inhibited by the inhibitors of ERK or JNK pathway. In conclusion, all these data showed that IGFBP5 could regulate Th17/Treg balance via ERK or JNK pathways. The findings of our study provide a theoretical basis for the application of IGFBP5 in inflammatory diseases.

Pyrroloquinoline Quinone Administration Alleviates Allergic Airway Inflammation in Mice by Regulating the JAK-STAT Signaling Pathway.

The current asthma therapies are inadequate for many patients with severe asthma. Pyrroloquinoline quinone (PQQ) is a naturally-occurring redox cofactor and nutrient that can exert a multitude of physiological effects, including anti-inflammatory and antioxidative effects. We sought to explore the effects of PQQ on allergic airway inflammation and reveal the underlying mechanisms. In vitro, the effects of PQQ on the secretion of epithelial-derived cytokines by house dust mite- (HDM-) incubated 16-HBE cells and on the differentiation potential of CD4+ T cells were investigated. In vivo, PQQ was administered to mice with ovalbumin- (OVA-) induced asthma, and lung pathology and inflammatory cell infiltration were assessed. The changes in T cell subsets and signal transducers and activators of transcription (STATs) were evaluated by flow cytometry. Pretreatment with PQQ significantly decreased HDM-stimulated thymic stromal lymphopoietin (TSLP) production in a dose-dependent manner in 16-HBE cells and inhibited Th2 cell differentiation in vitro. Treatment with PQQ significantly reduced bronchoalveolar lavage fluid (BALF) inflammatory cell counts in the OVA-induced mouse model. PQQ administration also changed the secretion of IFN-γ and IL-4 as well as the percentages of Th1, Th2, Th17, and Treg cells in the peripheral blood and lung tissues, along with inhibition the phosphorylation of STAT1, STAT3, and STAT6 while promoting that of STAT4 in allergic airway inflammation model mice. PQQ can alleviate allergic airway inflammation in mice by improving the immune microenvironment and regulating the JAK-STAT signaling pathway. Our findings suggest that PQQ has great potential as a novel therapeutic agent for inflammatory diseases, including asthma.

γ-Tocotrienol inhibits T helper 17 cell differentiation via the IL-6/JAK/STAT3 signaling pathway

γ-Tocotrienol (GT3), a member of the vitamin E family, is well known for its medicinal value in clinical treatments. However, the role of GT3 in T helper 17 (Th17)/regulatory T cell (Treg) differentiation and function is not fully understood. Here, we demonstrated that GT3 suppressed Th17 differentiation in vitro by inhibiting signal transducer and activator of transcription 3 (STAT3) phosphorylation in the interleukin 6 (IL-6)/Janus kinase (JAK)/STAT3 signaling pathway. GT3 also inhibited HIF1A expression in Th17 metabolism. Additionally, we showed that GT3 treatment inhibited disease aggravation in an imiquimod (IMQ)-induced psoriasis-like mouse model by reducing the percentage of Th17 cells in the spleen in vivo. The findings of this study demonstrated the effects of GT3 on Th17 cells through the STAT3 signaling pathway.

Educational Lecture 1 - Role of Innate and Adaptive Immunity in Endometriosis

Endometriosis is a multifactorial disease that mainly affects women of reproductive age and is associated with chronic pelvic pain and infertility. The exact pathogenesis of this disease is still debatable. In 2010, we established “bacterial contamination hypothesis”, a new concept in endometriosis. As a component of innate immunity, the role of bacterial endotoxin (lipopolysaccharide, LPS) and Toll-like receptor 4 (TLR4) in endometriosis was investigated and the possible source of endotoxin in uterine and pelvic environment was examined. We found that LPS regulates the pro-inflammatory response in pelvis and growth of endometriosis via LPS/TLR4 cascade. The highly contaminated menstrual blood with Escherichia coli was associated with significantly higher levels of endotoxin in the menstrual fluid and peritoneal fluid collected from women with endometriosis than that in control women. Most recently we examined the hypothesis that antibiotic treatment with or without GnRHa may decrease IUMC with reduction of inflammation and cell growth in women with endometriosis. We will report our current findings on this issue. The innate immunity and adaptive immunity are integral part of immune system. As a component of adaptive immunity, regulatory T (Treg) cells and T-helper-17 (Th17) cells may be involved in endometriosis. A reciprocal balance between Treg and Th17 cells may promote or retard the growth of endometriosis. Our knowledge on the changes in the percentages of Treg and Th-17 cells in the peripheral blood and in the peritoneal fluid of women with early and advanced endometriosis in unclear. We will report our current findings on this issue.

A mouse model of irradiation and spleen-thymus lymphocyte infusion induced aplastic anemia

ABSTRACT Objectives The immune-induced aplastic anemia (AA) mouse model has been used for the study of AA. However, there were no uniform conditions for establishing a model and no assessment of immunological homeostasis. Our study aimed to identify the conditions of establishing a model and assess the AA model in immunology and pathology. Methods We induced an AA mouse model by the combination between sublethal irradiation and spleen-thymus lymphocyte infusion. The success of establishing the AA model was identified by blood routine tests and pathology of bone marrow. The frequency of Th17 and Treg cells was measured by flow cytometry. The frequency of CD34+ and CD41+ cells was detected by immunohistochemical technique.IL-6, IL-8, IL-17, TNF-α and IFN-γ were evaluated by ELISA. Results The 137Cs sublethal irradiation (5 Gy) and spleen-thymus lymphocyte infusion (5 106) induced the AA mouse model successfully. The AA mice had a long lifetime and manifested pancytopenia and bone marrow failure. The percentage of Th17 cells increased and the percentage of Treg cells decreased distinctly in AA mice. The area of hematopoietic tissues and count of CD34+ cells and CD41+ cells were significantly reduced in AA mice.The level of cytokines, IL-6, IL-8, IL-17, TNF-α and IFN-γ, was increased significantly in peripheral blood and bone marrow. Conclusion Our data suggest that the improved AA mouse model conforms to the diagnosis standard of AA and simulates the immune internal environment of human AA. The AA mouse model has a longer lifetime and unbalances of Th17/Treg cells caused the destruction of CD34+ cells and CD41+ cells, which was immune-mediated pathogenesis to adapt to long-term research.

MDSCs Aggravate the Asthmatic Progression in Children and OVA-Allergic Mice by Regulating the Th1/Th2/Th17 Responses.

Background Asthma is a chronic inflammatory disease of respiratory with serious risks for children. This study explored myeloid-derived suppressor cells (MDSCs) on the pathogenesis of asthmatic children and mice. Methods The clinical study enrolled 30 asthma, 20 pneumonia, and 20 control participants. The MDSCs, Th17 and Th1 cells percentage, and IL-4, IL-12, IL-10, and IFN-γ levels were detected by flow cytometry and ELISA. In experimental asthma, mice were divided into control, ovalbumin (OVA), and OVA + MDSCs groups. The changes in inflammatory cell count and the levels of IL-5, IL-12, and IL-10 in mice BALF and the levels of inflammatory factors, IgE, and IFN-γ in mice were detected by ELISA. The amount of ROS generation and pathological changes and the levels of caspase 1 and caspase 3 were tested by flow cytometry, HE and PAS staining, and immunohistochemistry. The expression of cleaved caspase 1/caspase 1 and cleaved caspase 3/caspase 3 was detected by western blot. Results In clinical trials, the levels of IL-12, IFN-γ, and Th1 percentage decreased in pneumonia and asthma children's peripheral blood, while the levels of IL-4 and IL-10 and the percentages MDSCs and Th17 increased. In asthma mice, pathological staining showed that asthma caused lung inflammation and damage, while the OVA + MDSC group was severer. Moreover, the percentages of eosinophils, neutrophils, lymphocytes, and the levels of inflammatory factors, IgE, ROS production, caspase 1, caspase 3, cleaved caspase 1/caspase 1, and cleaved caspase 3/caspase 3 increased in OVA + MDSC group, while the percentage of macrophages, IL-12, and IFN-γ levels reduced, illustrating that MDSCs exacerbated asthma. Conclusion Our study indicated that MDSCs could aggravate asthma by regulating the Th1/Th2/Th17 response.

Infusion of two-dose mesenchymal stem cells is more effective than a single dose in a dilated cardiomyopathy rat model by upregulating indoleamine 2,3-dioxygenase expression

Background and aimsThe therapeutic efficacy of single-dose mesenchymal stromal cell (MSC) therapy for heart failure (HF) remains inconsistent. This study aimed to investigate whether infusion with two-dose human umbilical cord MSC (hUCMSCs) could be therapeutically superior to single-dose therapy in a rat model of dilated cardiomyopathy (DCM) and explored the underlying mechanisms.MethodsMale Sprague–Dawley rats were intraperitoneally injected with doxorubicin (DOX) to establish a DCM model and randomized to intravenously receive single-dose or two-dose hUCMSCs at an interval of 14 days. Their left ventricular (LV) systolic and diastolic functions were analyzed by echocardiography. The percentages of Th1, Th2, Th17, and Treg cells in the heart, spleen, lymph nodes, and peripheral blood and the levels of serum cytokines in individual rats were analyzed by flow cytometry and cytometric bead assay, respectively. The degrees of cardiac fibrosis and cardiomyocyte apoptosis were examined by histology. The importance of indoleamine 2,3-dioxygenase (IDO), an activator of Treg differentiation, in the therapeutic effect of hUCMSCs on inflammation and heart function of rats was determined after induction of IDO over-expression (IDO-OE) using IFN-γ (1 ng/ml) and TNF-α (10 ng/ml) stimulation or silencing (IDO-KD) using small interfering RNA (siRNA) technology.ResultsCompared with the single dose, two-dose hUCMSCs were more effective in improving LV performance, attenuating cardiac dilation, reducing cardiomyocyte apoptosis and cardiac fibrosis. Two-dose hUCMSC therapy significantly increased Treg number in the heart and peripheral blood, accompanied by increased cardiac IDO expression. Compared with the control hUCMSCs, IDO-OE hUCMSCs significantly enhanced Treg and Th2 cell responses and decreased systemic Th17 cell responses and Th1 cell numbers in the mediastinal lymph nodes. Treatment with IDO-OE hUCMSCs significantly improved LV remodeling and dysfunction. However, treatment with IDO-KD hUCMSCs had opposite effects in rats.ConclusionsAdministration of two-dose hUCMSCs has better therapeutic effects than single-dose therapy for inhibiting myocardial inflammation to improve LV function in DCM rats. These effects are associated with upregulating IDO expression and its systemic anti-inflammatory activities.

Imbalance of Th17, Treg, and helper innate lymphoid cell in the peripheral blood of patients with rheumatoid arthritis

IntroductionRheumatoid arthritis (RA) is a chronic inflammatory disease involving a variety of immune cells, including adaptive T and B cells and innate lymphoid cells (ILCs). Understanding the pathogenic role of these immune cells in RA provides new insights into the intervention and treatment of RA.MethodsA total of 86 patients with RA (RA group) and 50 healthy controls (HC) were included in the study. The immune cells of CD4+, CD19+ B, NK, Th17, Treg, ILCs, and their subsets (i.e., ILC1s, ILC2s, and ILC3s) were characterized in peripheral blood mononuclear cells by flow cytometry. Cytokines (i.e., IFN-γ, IL-4, IL-10, IL-17A, IL-22, and IL-33) in sera were detected using ELISA. The above immune cells and cytokines were analyzed in patients with different disease activity status and positive ( +) or negative ( −) rheumatoid factor (RF)/anti-citrullinated protein antibodies (ACPA).ResultsPatients with RA had higher percentages of CD4+ T, CD19+ B, Th17, ILC2s, and ILC3s and lower percentages of Treg and ILC1s than HC. Patients with RA had elevated levels of IFN-γ, IL-4, IL-17A, and IL-22 and decreased level of IL-10. Compared with HC, patients with high disease activity had higher percentages of Th17, ILC2s, and ILC3s; lower percentages of ILC1s; and lower level of IL-10. The percentage of Treg cells in remission, low, moderate, and high disease activities decreased, whereas the level of IL-17A increased compared with HC. Furthermore, RF+ or ACPA+ patients exhibited elevated percentages of CD19+ B, ILC2s, and ILC3s and had decreased percentage of ILC1s and Treg cells than HC. The percentage of Th17 cells increased in RF−/ACPA− and RF+/ACPA+ patients. However, the above immune cells between RF or ACPA positive and negative patients were not significantly different.ConclusionTh17, Treg, and ILC subset dysregulations are present in patients with RA but may not be associated with conventionally defined seropositive RF and ACPA.Key Points• Th17, Treg, and ILC subset dysregulations are present in patients with RA but may reflect inflammation rather than specific diseases and stages.• No difference for the distribution of Th17, Treg, and ILC subsets between RF+and RF− patients and between ACPA+and ACPA− patients. The screening spectrum of RF and ACPA serology should be expanded to elucidate the role of immune cells in RA pathogenesis.

SARS-CoV-2-Specific Adaptive Immunity in COVID-19 Survivors With Asthma.

BackgroundAsthma patients potentially have impaired adaptive immunity to virus infection. The levels of SARS-CoV-2-specific adaptive immunity between COVID-19 survivors with and without asthma are presently unclear.MethodsCOVID-19 survivors (patients with asthma n=11, with allergies n=8, and COVID-19 only n=17) and non-COVID-19 individuals (asthmatic patients n=10 and healthy controls n=9) were included. The COVID-19 patients were followed up at about 8 months and 16 months after discharge. The clinical characteristics, lymphocyte subsets, memory T cells, and humoral immunity including SARS-CoV-2 specific antibodies, SARS-CoV-2 pseudotyped virus neutralization assay, and memory B cells were analyzed in these subjects.ResultsThe strength of virus-specific T cell response in COVID-19 survivors was positively correlated with the percentage of blood eosinophils and Treg cells (r=0.4007, p=0.0188; and r=0.4435, p=0.0086 respectively) at 8-month follow-up. There were no statistical differences in the levels of SARS-CoV-2-specific T cell response between the COVID-19 survivors with, and without, asthma. Compared to those without asthma, the COVID-19 with asthma survivors had higher levels of SARS-CoV-2-specific neutralizing antibodies (NAbs) at the 8-month follow-up (p<0.05). Moreover, the level of NAbs in COVID-19 survivors was positively correlated with the percentage of Treg and cTfh2 cells (r=0.5037, p=0.002; and r=0.4846, p=0.0141), and negatively correlated with the percentage of Th1 and Th17 cells (r=-0.5701, p=0.0003; and r=-0.3656, p=0.0308), the ratio of Th1/Th2, Th17/Treg, and cTfh1/cTfh2 cell (r=-0.5356, r=-0.5947, r=-0.4485; all p<0.05). The decay rate of NAbs in the COVID-19 survivors with asthma was not significantly different from that of those without asthma at 16-month follow-up.ConclusionThe level of SARS-CoV-2-specific NAbs in COVID-19 survivors with asthma was higher than that of those without asthma at 8-month follow-up. The SARS-CoV-2-specific T cell immunity was associated with blood eosinophils and Treg percentages. The SARS-CoV-2-specific humoral immunity was closely associated with cTfh2/cTfh1 imbalance and Treg/Th17 ratio. According to the findings, asthmatic patients in COVID-19 convalescent period may benefit from an enhanced specific humoral immunity, which associates with skewed Th2/Th1 and Treg/Th17 immune.

JNK pathway-associated phosphatase in acute ischemic stroke patients: Its correlation with T helper cells, clinical properties, and recurrence risk.

ObjectiveJKAP modifies T‐cell immune response and inflammation, also involves in cardia‐cerebrovascular disease etiology. This study intended to explore JKAP's relation with T‐helper 1 (Th1), T‐helper 17 (Th17) cell levels, clinical properties, and recurrence‐free survival (RFS) in acute ischemic stroke (AIS) patients.MethodsA total of 155 AIS patients were analyzed. Serum JKAP, interferon‐gamma (IFN‐γ), and interleukin‐17A (IL‐17A) were detected by ELISA; then blood Th1 and Th17 cells were quantified by flow cytometry. Besides, 30 healthy subjects were enrolled as controls to detect JKAP, Th1, and Th17 cells.ResultsJKAP level was lower (p < 0.001), Th1 cells were not differed (p = 0.068), but Th17 cells were elevated in AIS patients versus controls (p < 0.001). Meanwhile, JKAP was negatively correlated with Th1 cells (p = 0.038), Th17 cells (P<0.001), IFN‐γ (p = 0.002), and IL‐17A (p < 0.001) in AIS patients. JKAP was negatively associated with the National Institutes of Health Stroke Scale (NIHSS) score (p < 0.001), but Th17 cells (p = 0.001), IFN‐γ (p = 0.035), and IL‐17A (p = 0.008) levels were positively associated with NIHSS score. Additionally, accumulating RFS was numerically longer in patients with JKAP Quantile (Q) 4 than patients with JKAP Q1–Q3 (p = 0.068), and numerically better in patients with JKAP Q3–Q4 than patients with JKAP Q1–Q2 (p = 0.069), but without statistical significance.ConclusionJKAP correlates with lower Th1 and Th17 cell percentages as well as milder disease severity.

Changes of Peripheral Th17 Cells Subset in Overweight and Obese Children After Body Weight Reduction.

BackgroundObesity has been a growing problem in young patients leading to serious metabolic complications. There are many studies supporting the idea, that obesity should be considered as a chronic inflammation closely associated with immune system alterations. Th17 subpopulation is strongly involved in this process. The aim of our study was to evaluate circulating Th17 cells in overweight and obese children and explore the relationships between Th17 subset and metabolic parameters.MethodsWe evaluated peripheral Th17 cells in fresh peripheral blood samples from 27 overweight and obese and 15 normal-weight children. Th17 cells were identified by flow cytometry using monoclonal antibody and intracellular IL-17A staining. Th17 cells were defined as CD3+CD4+CD196+IL-17Aic+. The analysis involved anthropometric and metabolic parameters measured at baseline and three months after the change of lifestyle and diet. We evaluated the relationship between metabolic parameters and Th17 cells.ResultsIn overweight and obese children we found significantly higher Th17 cells percentage compared to normal weight controls (median 0.097% (0.044 - 0.289) vs 0.041% (0.023 - 0.099), p = 0.048). The percentage of Th17 cells decreased statistically significantly in children who reduced weight after the intervention (0.210% (0.143 - 0.315) vs 0.039% (0.028 - 0.106), p = 0.004). In this group we also noticed statistically significant reduction of TC and LDL-C concentration (p = 0.01, p = 0.04, respectively).ConclusionsObesity in children is associated with increased percentage of peripheral Th17 cells. Weight reduction leads to significant decrease of circulating Th17 cells and improvement of lipid parameters. This significant reduction of proinflammatory Th17 cells is a promising finding suggesting that obesity-induced inflammation in children could be relatively easily reversible.

Dynamic Immune Function Changes Before and After the First Radioactive Iodine Therapy After Total Resection of Differentiated Thyroid Carcinoma.

The effects of total thyroidectomy or radioactive iodine therapy on immune activation and suppression of the tumor microenvironment remain unknown. We aimed to investigate the effects of these treatments on the immune function in patients with differentiated thyroid carcinoma (DTC). Our cohort included 45 patients with DTC treated with total thyroidectomy and radioactive iodine therapy (RAIT). Immune function tests were performed by flow cytometry at 0, 30, and 90 days post-RAIT. Both the percentage and absolute number of circulating regulatory T cells were significantly lower in the postoperative DTC compared to the healthy controls. Notably, the absolute number of multiple lymphocyte subgroups significantly decreased at 30 days post-RAIT compared to those pre-RAIT. The absolute counts of these lymphocytes were recovered at 90 days post-RAIT, but not at pre-RAIT levels. Additionally, the Th17 cell percentage before RAIT was positively correlated with thyroglobulin (Tg) levels after RAIT. The tumor burden might contribute to increased levels of circulating Tregs. In conclusion, RAIT caused transient radiation damage in patients with DTC and the percentage of Th17 cells before RAIT could be a significant predictor of poor prognosis in patients with DTC.

Cell division control protein 42 correlates with lower disease risk and its elevation predicts better treatment response, and inhibits T-helper 17 cell differentiation in rheumatoid arthritis.

Previous research reports that cell division control protein 42 (CDC42) is dysregulated in rheumatoid arthritis (RA). This study aimed to further explore the linkage of CDC42 with T-helper (Th) 1 and Th17 cell differentiation, and its implication in RA management. After enrolling 80 RA patients, their blood CDC42, Th1 and Th17 cells were detected by RT-qPCR and flow cytometry, respectively, IFN-γ and IL-17A were detected by ELISA. Based on the treatment response at week 12, the patients were classified as response patients and no response patients. In addition, blood CDC42 was also detected after enrolling 40 healthy controls. Subsequently, naïve CD4+ T cells from RA patients were transfected with control, CDC42 overexpression and knockdown lentivirus, followed by differentiation assay. CDC42 was reduced in RA patients versus healthy controls (P < 0.001). In RA patients, CDC42 was negatively correlated with IFN-γ (P = 0.023), Th17 cells (P = 0.011) and IL-17A (P = 0.003) but not Th1 cells (P = 0.200). CDC42 presented an increasing trend after treatment (P < 0.001); besides, CDC42 at week 8 (P = 0.027) and week 12 (P < 0.001) were increased in response patients versus no response patients. Subsequent experiment showed that in RA CD4+ T cells, CDC42 overexpression reduced IFN-γ and IL-17A (both P < 0.05), while CDC42 knockdown elevated IL-17A (P < 0.05) but not IFN-γ (P > 0.05). Moreover, CDC42 overexpression inhibited, while CDC42 knockdown increased Th17 cell percentage (P < 0.05) but not Th1 cell percentage (P > 0.05). CDC42 negatively correlates with disease risk and its elevation predicts better treatment response; it also inhibits Th17 but not Th1 cell differentiation in RA.

Effects of treatment with methimazole on circulating CD4+ and CD8+ Tcells positive for programed cell death protein-1 and on subsets of CD4+ Tcells in untreated hyperthyroid patients with Graves' disease.

We investigated longitudinal changes in circulating CD4+ and CD8+ Tcells positive for programed cell death protein-1 (PD-1) and in other subsets of CD4+ Tcells in untreated hyperthyroid patients with Graves' disease after treatment with methimazole (MMI). The study included 18 untreated hyperthyroid patients with Graves' disease and 18 age-matched controls. Before and after 12-week treatment with MMI, we used flow cytometry to measure circulating PD-1+ D4+ and PD-1+ CD8+ Tcells and subsets of CD4+ Tcells in peripheral blood, as well as serum levels of chemokines related to T-helper type 1 (Th-1) and Th-2 cells. At baseline, the percentage of CD4+ and CD8+ Tcells expressing PD-1 was significantly higher in patients than in age-matched controls. Serum levels of chemokines related to Th-1 and Th-2 also were higher in patients. Twelve weeks after initiation of MMI, the percentage of CD4+ Tcells expressing PD-1 was significantly lower than at baseline, but no such change was seen in CD8+ Tcells. Furthermore, the percentage of Th-1 cells among CD4+ Tcells and the serum levels of soluble CD26/dipeptidyl peptidase-4, a surface marker of Th-1 cells, also were significantly lower than at baseline. The expression of PD-1 on circulating CD4+ and CD8+ Tcells is increased in hyperthyroid patients with active Graves' disease. MMI significantly decreases levels of circulating PD-1+ CD4+ Tcells, suggesting that PD-1+ Tlymphocytes may be associated with the pathogenesis of Graves' disease.

LncRNA FR215775 Regulates Th2 Differentiation in Murine Allergic Rhinitis.

To identify the effect of long noncoding RNA (lncRNA) FR215775 in regulating CD4+ T cells on murine models of allergic rhinitis (AR), the expression of lncRNA FR215775 in primary Th2 cells was detected through qRT-PCR. After knocking down the expression of lncRNA FR215775 via Sh-FR215775-Ads, Cell Counting Kit-8, cytometric bead array, and fluorescence-activated cell sorting were performed to determine its functions in vitro. Moreover, lncRNA FR215775-silencing or nonsilencing cells were injected intravenously into AR mice. Then, hematoxylin and eosin, Alcian blue-periodic acid Schiff, and toluidine blue staining were performed, and the levels of IL-2, IL-4, IL-5, IL-6, IL-10, IL-17A, IFN-γ, and TNF in the AR mice were also determined. We found that the expression of lncRNA FR215775 was specifically higher in the murine primary Th2 cells. After the knockdown of lncRNA FR215775, the proliferation of CD4+ T cells was inhibited, and the expressions of IL-4 and IL-5 in the cell culture supernatant were significantly decreased (P < 0.001), along with the percentage of Th2 cells (P < 0.05). The lncRNA FR215775-silencing AR group showed less serious allergic symptoms and a low level of ovalbumin-specific immunoglobulin E (P < 0.01). Meanwhile, the eosinophilia inflammation, goblet cell hyperplasia, and mast cell inflammation in the nasal mucosa all decreased, which indicated attenuated allergic inflammation in the lncRNA FR215775-silencing AR group. In addition, the Th2-related cytokines IL-4 and IL-5 were downregulated in the serum and nasal lavage fluid of this group (P < 0.01). In conclusion, lncRNA FR215775 may play a vital role in the function and differentiation of Th2 cells, which may encourage allergic inflammation. These results may provide significant insights into AR pathogenesis and offer new treatment targets for alleviating AR.