Th17 Cells In Patients Research Articles

Profile of Inflammatory Cytokines in Gingival Crevicular Fluid and Plasma in Patients With Grade C Periodontitis During Orthodontic Treatment: A Longitudinal Case Series Report.

To examine the immune responses in patients diagnosed as grade C periodontitis during orthodontic treatment. Our study included seven orthodontic patients with grade C periodontitis and measured their levels of inflammatory cytokines in gingival crevicular fluid and plasma before orthodontic treatment, during the alignment and levelling phase, and during the detailing and finishing phase. The key signal pathways in the orthodontic process of patients with periodontitis were detected by KEGG analysis. Studies have shown that orthodontic treatment brings great improvement to patients with grade C periodontitis, and most of the local/systemic inflammatory cytokines can be reduced after orthodontic treatment. Simultaneously, orthodontic treatment can reduce the percentage of IFN-γ+ Th1 cells in patients with grade C periodontitis. Through KEGG analysis, the IL-17 signalling pathway and TNF signalling pathway are closely interrelated in the orthodontic treatment of patients diagnosed with grade C periodontitis (p-value < 0.001). Orthodontic treatment can effectively control the local and system levels of inflammation in patients with grade C periodontitis, with IL-17A and TNF-α as potential distinctive inflammatory markers for orthodontic-periodontal combined treatment in individuals with periodontitis.

Effect of anesthetic technique on antitumor immunity in patients undergoing surgery for gall bladder cancer: A prospective randomized comparative study.

There is a paucity of literature regarding the effect of anesthetic techniques on antitumor immunity, especially in gall bladder malignancies. We designed a study to compare the effect of propofol-based total intravenous anesthesia and sevoflurane-based general anesthesia-on antitumor immunity, including tumor growth factor-β (TGF-β), T-helper cell profile, and inflammatory markers. A pilot prospective randomized trial was conducted in 64 patients undergoing surgery for gall bladder malignancy under general anesthesia in a tertiary specialty cancer hospital. Adult cancer patients of ASA physical status I-III fulfilling the inclusion criteria were randomized to either group S (sevoflurane-based general anesthesia) or group T (propofol-based total intravenous anesthesia). Preoperative (morning of surgery) and postoperative (24 h and 1 month after surgery) blood samples were obtained. Demographic profile and preoperative parameters were comparable between both groups. There was a statistically significant difference in the postoperative value of TGF-β (higher in group T). There was a statistically significant difference in postoperative interleukin-17A value (indicative of TH17 cells), and it was found to be higher in group S. Propofol-based TIVA increases serum TGF-β levels. At the same time, Sevoflurane modulates T-helper cells-based immunity to increase TH17 cells in patients with gall bladder cancer. Multiple larger studies will be required to validate the results and provide useful recommendations.

CD226 implicated in Akt-dependent apoptosis of CD4+ T cell contributes to asthmatic pathogenesis.

Asthma is a chronic airway inflammatory disease in which CD4+ T cell dysregulation occurs. Here, we investigated the molecular role and clinical significance of CD226, a costimulatory molecule of T lymphocytes, in the development of allergic asthma. Our results revealed that the expression of CD226 was significantly increased in CD4+ effector T cells, especially in T helper (Th) 2 cells and Th17 cells in patients with asthma. Moreover, CD4+ T cell-specific Cd226-knockout mice were generated and together with littermates were challenged with ovalbumin (OVA) to establish a model of allergic asthma. We found that CD226 deficiency in CD4+ T cells mitigated lung inflammation, IgE production, and eosinophil infiltration and reduced airway remodeling in experimental allergic asthma. However, the impact of CD226 on asthma was independent of Treg cell modulation. Through RNA-seq data analysis, the apoptosis pathway was screened. Mechanistically, CD226 deletion promoted CD4+ T cell late apoptosis via the activation of Caspase-3 in an Akt-dependent manner. Furthermore, blocking CD226 signaling with a recombinant fusion protein attenuated asthma features in mice and achieved a good therapeutic effect. Overall, this study revealed a unique role of CD226 in CD4+ T cell regulation in asthma pathogenesis. Therefore, targeting CD226 may provide new insights into the clinical treatment of asthma.

Th17 pathway‐related immune signatures in the pathobiology of myasthenia gravis: Integrating the roles of regulatory/effector cytokines and transcription factors

AbstractObjectivesMyasthenia gravis (MG) is an autoimmune disorder mediated by antibodies against the acetylcholine receptor (AChR), muscle specific kinase (MuSK), and other antigens in the neuromuscular junction. Antibody production is influenced by T lymphocytes. The T helper 17 (Th17) subset, an inflammatory lineage of Th cells, is associated with several autoimmune diseases. Functional interactions between T lymphocytes and pathogenic antibody responses including aberrant Th17 cell responses have been reported in MG. However, the precise mechanism(s) underlying the activation and/or pathogenic transformation of Th17 cells are not clearly known. The current study aimed at simultaneously exploring the roles of the inducers, master regulator transcription factors, and effectors of Th17 cells in patients with MG.MethodsIn this cross‐sectional study, quantification of gene expression of IL6, IL17A, STAT3, and RORC in the peripheral mononuclear cells by quantitative polymerase chain reaction (qPCR) as well as estimation of plasma levels of IL‐1β, IL‐6, and IL‐17A cytokines by multiplex suspension assay were carried out in 59 patients with MG and 61 healthy controls.ResultsGene expression levels of IL17A were significantly upregulated in patients as compared to healthy controls. The plasma levels of IL‐1β, IL‐6, and IL‐17A were significantly elevated in patients compared to healthy controls. IL17A as well as RORC gene expressions correlated with the clinical features. IL17A gene expression levels were higher in AChR‐MG patients.ConclusionThe present study supports the crucial role of the Th17 pathway in the pathobiology of MG, including its potential influence on disease severity.

Analysis of Th17 cell population and expression of microRNA and factors related to Th17 in patients with premature ovarian failure

Folliculogenesis is the process where follicles in the ovaries develop and eventually lead to ovulation. Any disruption to this process can cause premature ovarian failure. miR-326 is one of the microRNAs whose expression leads to Th17 production. Th17 activates the immune system to respond more vigorously, and by producing interlukins and cytokines causes inflammation and autoimmune disorders. Th17-induced inflammation and Th17/Treg imbalance can result in POF. This investigation took samples from 30 POF patients and 30 healthy people. The study utilized PCR to assess the expression levels of cytokines, specific transcription factor (ROR-γt), and miR-326. Additionally, ELISA was employed to analyze serum levels of IL-17, IL-21, IL-23. Furthermore, flow cytometry was utilized to determine the frequency of Th17. Compared to the control group, our results demonstrated a rise in the transcription factor RORɣt and a considerable rise in the frequency of Th17 cells in patients with POF. The level of inflammatory cytokines IL-17, IL-21, and IL-23 secreted in serum samples of patients with POF increased significantly compared to the control group. Results of investigating microRNA associated with Th17 cells also showed increased expression of miR-326 in females suffering from POF. The elevation of pro-inflammatory markers in women with POF contrary to the control group underscores the significant involvement of the immune system in pregnancy disorders pathogenesis. Consequently, immunological factors may serve as promising biomarkers for predicting POF likelihood in high-risk women in the future.

Allergens induce upregulated IL-18 and IL-18Rα expression in blood Th2 and Th17 cells of patients with allergic asthma.

Allergic asthma (AA) is closely associated with the polarization of T helper (Th)2 and Th17 cells. Interleukin (IL)-18 acts as an inducer of Th2 and Th17 cell responses. However, expressions of IL-18 and IL-18 receptor alpha (IL-18Rα) in blood Th2 and Th17 cells of patients with AA remain unclear. We therefore investigated their expressions in Th2 and Th17 cells using flow cytometric analysis, quantitative real-time PCR (qPCR), and murine AA model. We observed increased proportions of Th2, Th17, IL-18+, IL-18+ Th2, and IL-18+ Th17 cells in blood CD4+ T cells of patients with AA. Additionally, house dust mite seemed to upregulate further IL-18 expression in Th2 and Th17, and upregulate IL-18Rα expression in CD4+ T, Th2, and Th17 cells of AA patients. It was also found that the plasma levels of IL-4, IL-17A, and IL-18 in AA patients were elevated, and they were correlated between each other. In ovalbumin (OVA)-induced asthma mouse (AM), we observed that the percentages of blood CD4+ T, Th2, and Th17 cells were increased. Moreover, OVA-induced AM expressed higher level of IL-18Rα in blood Th2 cells, which was downregulated by IL-18. Increased IL-18Rα expression was also observed in blood Th2 cells of OVA-induced FcεRIα-/- mice. Collectively, our findings suggest the involvement of Th2 cells in AA by expressing excessive IL-18 and IL-18Rα in response to allergen, and that IL-18 and IL-18Rα expressing Th2 cells are likely to be the potential targets for AA therapy.

Increased interleukin-9 and Th9 cells in patients with refractory Graves' disease and interleukin-9 polymorphisms are associated with autoimmune thyroid diseases.

Autoimmune thyroid diseases (AITDs) are prevalent disorders, primarily encompassing Graves' disease (GD) and Hashimoto's thyroiditis (HT). Despite their common occurrence, the etiology of AITDs remains elusive. Th9 cells, a new subset of CD4+T cells with immunomodulatory properties, have been linked to the development of various autoimmune diseases. However, research on the role of Th9 cells in AITDs is limited. We investigated the expression of Th9 cells,their functional cytokine IL-9, and transcription factor IRF4 in peripheral blood mononuclear cells (PBMCs) and plasma of AITD patients and healthy controls. Additionally, we explored the genetic association between four loci polymorphisms (rs31564, rs2069879, rs1859430, and rs2069868) of the IL-9 gene and AITDs. We reported, for the first time, that refractory GD patients exhibited elevated mRNA levels of IL-9 and IRF4 in PBMCs, increased IL-9 protein levels in plasma, and a higher proportion of Th9 cells in peripheral blood when compared to normal controls. Furthermore, human recombinant IL-9 protein was found to enhance IFN-g secretion in PBMCs from both GD patients and normal controls. At the genetic association level, after adjusting for age and sex, the rs2069879 polymorphism exhibited a significant association with AITDs under an additive model (P<0.001, OR= 0.05, 95% CI=0.03-0.08). Our results reveal that Th9 cells may exert a pivotal role in the pathogenesis and progression of refractory GD and HT, and IL-9 holds promise as a novel therapeutic target for the management of AITDs.

P981 Risankizumab, but not ustekinumab or vedolizumab, downregulates IL-23-induced mucosal pathogenic Th17 cells in patients with Crohn’s disease

Abstract Background We recently described an interleukin(IL)-23-inducible pathogenic subset of CCR6+CXCR3-CCR5+ mucosal T helper (Th)17 cells (pTh17) infiltrating Crohn’s disease (CD) inflamed mucosa and specifically activated in response to Adherent-Invasive Escherichia Coli. pTh17 cells are functionally and phenotypically distinct from CCR6+CXCR3-CCR5- Th17 cells (cTh17) and from IL-12-induced CCR6+CXCR3+ Th1/17 subset. Here, we investigated pTh17 cells' recirculation into the bloodstream, localization into the intraepithelial lymphocyte (IEL) compartment, and in-vivo modulation by different biological therapies. Methods Adult patients with active CD initiating either vedolizumab as per clinical practice or ustekinumab and risankizumab during the SEQUENCE trial were prospectively recruited at Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano. In vedolizumab-treated patients, peripheral blood and intestinal biopsies were collected at baseline and at the end of induction. In ustekinumab- and risankizumab-treated patients, intestinal biopsies were collected outside study protocol assessments at baseline and week 24. Endoscopic response was defined as a greater than 50% decrease in the Simple Endoscopic Score from baseline. Peripheral blood mononuclear cells, lamina propria mononuclear cells (LPMC), and IEL were isolated and analyzed through flow cytometry. Results Overall, 34 CD patients were assessed. Demographic and baseline disease characteristics are summarized in Table 1. At baseline, as compared with cTh17, pTh17 cells: 1. are rarely found in the peripheral blood and express low levels of CCR9 and α4β7, 2. express high levels of tissue-resident markers CD69+CD103+ in the mucosa, and 3. infiltrate the IEL layer upon binding of CD103 with E-cadherin. Baseline pTh17 cells were upregulated in patients not achieving vedolizumab-induced endoscopic response. Upon vedolizumab treatment, a selective downregulation of mucosal cTh17 cells but not pTh17 was observed. Remarkably, risankizumab induced a specific downregulation of pTh17 cells, but not cTh17, in both LPMC and IEL layers. Conversely, ustekinumab reduced Th1/17 mucosal subsets, but not pTh17 cells (Figure 1). Conclusion pTh17 cells are largely unable to recirculate through the bloodstream, express markers of gut-tissue residency, and infiltrate the IEL compartment. IL-23 neutralization by risankizumab specifically downregulates mucosal pTh17 cells, as compared with vedolizumab and ustekinumab. Our immunologic results might provide mechanistic clues to vedolizumab latency effect in CD, and potentially explain early signs of risankizumab superiority over ustekinumab in the SEQUENCE study in terms of endoscopic response at 24 weeks.

Allergen exposure boosts peripheral Th9 responses in patients with local allergic rhinitis.

Intranasal allergen exposure increases peripheral total Th2 and Th9 cells in patients with local allergic rhinitis (LAR). Peripheral T-cell response seems dominated by Th9 cells in patients with LAR, whereas Th2 responses prevail in patients with allergic rhinitis. Our results identify Th9 cells as potential therapeutic targets for patients with LAR.

Heat shock cognate 70 protein like-2 protein in camphor pollen is one of the major culprits of asthma.

In recent decades, Cinnamomum camphora have gradually become the main street trees in Shanghai. This study aims to investigate the allergenicity of camphor pollen. A total of 194 serum samples from patients with respiratory allergy were collected and analyzed. Through protein profile identification and bioinformatics analysis, we hypothesized that heat shock cognate protein 2-like protein (HSC70L2) is the major potential allergenic protein in camphor pollen. Recombinant HSC70L2 (rHSC70L2) was expressed and purified, and a mouse model of camphor pollen allergy was established by subcutaneous injection of total camphor pollen protein extract (CPPE) and rHSC70L2. Specific IgE was found in the serum of 5 patients in response to camphor pollen and three positive bands were identified by Western blotting. Enzyme-linked immunosorbent assay (ELISA), Immune dot blot and Western blot experiments confirmed that CPPE and rHSC70L2 can cause allergies in mice. Moreover, rHSC70L2 induces polarization of peripheral blood CD4+ T cells to Th2 cells in patients with respiratory allergies and mice with camphor pollen allergy. Finally, we predicted the T cell epitope of the HSC70L2 protein, and through the mouse spleen T cell stimulation experiment, we found that the 295EGIDFYSTITRARFE309 peptide induced T cells differentiation to Th2 and macrophages differentiation to the alternatively activated (M2) state. Moreover, 295EGIDFYSTITRARFE309 peptide increased the serum IgE levels in mice. The identification of HSC70L2 protein can provide novel diagnostic and therapeutic targets for allergies caused by camphor pollen.

Aberrant Naive CD4-Positive T Cell Differentiation in Systemic Juvenile Idiopathic Arthritis Committed to B Cell Help.

Systemic juvenile idiopathic arthritis (JIA) features characteristics of autoinflammation and autoimmunity, culminating in chronic arthritis. In this study, we hypothesized that aberrant or incomplete polarization of T helper cells contributes to disease pathology. Cells or serum samples were obtained from healthy controls (n=72) and systemic JIA patients (n=171). Isolated naive T helper cells were cultured under Th1, Th17, and T follicular helper (Tfh) or T peripheral helper (Tph)-polarizing conditions and were partly cocultured with allogenic memory B cells. Cell samples were then analyzed for surface marker, transcription factor, and cytokine expression, as well as plasmablast generation. Serum samples were subjected to multiplexed bead and self-antigen arrays and enzyme-linked immunosorbent assays, and all data were compared to retrospective RNA profiling analyses. Differentiation of systemic JIA-naive T helper cells toward Th1 cells resulted in low expression levels of interferon-γ (IFNγ) and eomesodermin, which was associated in part with disease duration. In contrast, developing Th1 cells in patients with systemic JIA were found to produce elevated levels of interleukin-21 (IL-21), which negatively correlated with cellular expression of IFNγ and eomesodermin. In both in vitro and ex vivo analyses, IL-21 together with programmed cell death 1 (PD-1), inducible T cell costimulator (ICOS), and CXCR5 expression induced naive T helper cells from systemic JIA patients to polarize toward a Tfh/Tph cell phenotype. Retrospective analysis of whole-blood RNA-sequencing data demonstrated that Bcl-6, a master transcription factor in Tfh/Tph cell differentiation, was overexpressed specifically in patients with systemic JIA. Naive T helper cells from systemic JIA patients which were stimulated in vitro promoted B cellular plasmablast generation, and self-antigen array data indicated that IgG reactivity profiles of patients with systemic JIA differed from those of healthy controls. In the pathogenesis of systemic JIA, skewing of naive T helper cell differentiation toward a Tfh/Tph cell phenotype may represent an echo of autoimmunity, which may indicate the mechanisms driving progression toward chronic destructive arthritis.

Correlation between B-cell lymphoma 6 with the balance of T helper-1/2 and severity of allergic rhinitis.

Allergic rhinitis (AR) is a prevailing immune disorder affecting the nasal mucosa. B-cell lymphoma 6 (BCL6) imposes essential roles in immunity. This study probed into the serum expression of BCL6 and its effect on AR diagnosis and patients' quality of life (QOL). A total of 113 patients with AR including 38 cases with mild AR (MAR) and 75 cases with moderate-severe AR (MSAR) were enrolled, with 101 healthy people enrolled as control. Serum expression of BCL6 was detected by RT-qPCR and the diagnostic efficacy of BCL6 for AR was analyzed using the receiver operating characteristic curve. The proportion of T helper-1/2 (Th1/Th2) cells in CD4+ T cells in peripheral blood mononuclear cells was detected using flow cytometry. The correlation between BCL6 and Th1/Th2 cells and the effects of BCL6 expression on patients' QOL were assessed by Pearson analysis and Mini-RQLQ questionnaire. BCL6 was downregulated in patients with AR, serum BCL6 level < 0.8450 had certain auxiliary diagnostic values for AR, and serum BCL6 level < 0.5400 could assist the diagnosis of AR severity. Th1 cell proportion in CD4+ T cells was decreased, whereas Th2 cell proportion was increased with AR severity. BCL6 was positively-linked with Th1 cells but inversely-correlated with Th2 cells in patients with AR. Patients with AR with low BCL6 expression had a poorer QOL compared with high BCL6 expression. The domains most affected by BCL6 expression were practical problems, nasal symptoms, and lacrimation. Serum BCL6 is downregulated and low BCL6 expression greatly deteriorates QOL in patients with AR.

The influence of &lt;i&gt;Aspergillus fumigatus&lt;/i&gt; micromycetes on immune response regulation in patients with asthma

Introduction. Aspergillus fumigatus is able not only to sensitize patients with atopy, but also to colonize the respiratory tract, remaining a constant source of allergens due to the small spore size and thermal tolerance. Currently, the role of micromycetes in the immunopathogenesis of asthma has been poorly studied. The objective was to evaluate the features of the immune response regulation in patients with allergic bronchopulmonary aspergillosis (ABPA) or asthma with sensitization to A. fumigatus. Materials and methods. There were enrolled 15 patients with ABPA, 10 patients with asthma with sensitization to A. fumigatus, 16 patients with asthma without sensitization to A. fumigatus. The control group consisted of 16 apparently healthy volunteers. All patients underwent a clinical and functional examination. The subpopulations of blood lymphocytes were assessed by flow cytometry. The A. fumigatus allergen was added to peripheral blood samples to evaluate the production of IFN, IL-10 and IL-13. The serum cytokine levels in cell culture supernatants, as well as total IgE, A. fumigatus-specific IgE (sIgE) as well as thymus and activation-regulated chemokine (TARC) level were measured by enzyme-linked immunosorbent assay. Results. Significantly higher serum levels of total IgE, A. fumigatus-specific sIgE and TARC were found in patients with ABPA and asthma with sensitization to A. fumigatus compared to patients with asthma without sensitization to A. fumigatus. The results of lymphocyte immunophenotyping revealed significant excess of memory Th2 cells and T-regulatory cells in all patients with asthma compared to the control group. The count of Tfh2 was higher but memory Th17.1 cells were lower in patients with sensitization to A. fumigatus compared to those of apparently healthy volunteers. Patients with ABPA had significantly higher count of memory Th2 cells and TARC level compared to patients with asthma sensitized to A. fumigatus. The increased activity of memory Th2 cells is confirmed by increased secretion of IL-13 and IL-10 following along with decreased IFN production in response to specific fungal allergen stimulation of blood cells compared to the patients with asthma and the control group. A positive correlation was revealed between the count of memory Th2 cells and the levels of sIgE, IgE, TARC, a negative correlation with FEV1. Conclusion. Thus, exposure to A. fumigatus significantly enhances the activity of memory Th2 cells in patients with asthma which can lead to severe disease course and development of allergic bronchopulmonary aspergillosis. The features of the immune response identified dictate a need for a personalized approach to choose therapeutic tactics in such patients.

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.

Levels of Pathogenic Th17 and Th22 Cells in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune condition characterized, among others, by tissue damage and activation/differentiation of proinflammatory lymphocytes. Accordingly, several studies have concluded that type 17 T helper (Th17) cells seem to have an important role in the pathogenesis of this condition. However, the strategy for the identification and analysis of proinflammatory Th17 cells in those studies has not been consistent and has usually been different from what was originally described. Therefore, we decided to evaluate the levels of Th17 cells in patients with RA employing an extended immune phenotype by using an eight-color multiparametric flow cytometry analysis. For this purpose, blood samples were obtained from 30 patients with RA and 16 healthy subjects, and the levels of Th17 and type 22 helper (Th22) lymphocytes were analyzed as well as the in vitro differentiation of peripheral blood mononuclear cells into Th17 lymphocytes induced by interleukin-23 (IL-23) and IL-1β. We found significant enhanced levels of total Th17 lymphocytes (defined as CD4+IL-17+) as well as enhanced numbers of their pathogenic (defined as CD4+CXCR3+IL-17+IL-22+CD243+CD161+IFN-γ+IL-10−) and nonpathogenic (CD4+CXCR3+IL-17+IL-22−CD243−CD161−IFN-γ−IL-10+) cell subsets in patients with RA. Likewise, the number of Th22 (CD4+CXCR3+/-IL-17−IL-22+) was also increased in these patients compared to healthy controls. However, the in vitro induction/differentiation of pathogenic Th17 cells showed similar results in controls and patients with RA. Likewise, no significant associations were detected in patients with RA between the levels of Th17 or Th22 cells and clinical or laboratory parameters. Our data indicate that patients with RA show enhanced blood levels of the different subsets of Th17 cells and Th22 lymphocytes tested in this study and suggest that these levels are not apparently associated with clinical or laboratory parameters.

IL-6 activates pathologic Th17 cell via STAT 3 phosphorylation in inflammatory joint of Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease, which is characterized by inflammation of the axial skeleton and the peripheral arthritis. An increase in the number of Th17 cells in patients with AS has been reported. Although Th17 cells have been involved in the induction of inflammation, recent data suggest that not all Th17 cells are pathogenic, showing regulatory function of Th17 cell. Cells producing both interferon-gamma (IFN-γ) and interleukin (IL)-17 have been reported to be the main pathologic Th17 (pTh17) cells that induce inflammation at sites of joint. Emerging evidence demonstrated that IL-6 has a main role in regulating the balance between inflammatory and regulatory T cells. However, there is no direct study to assess pTh17 cell with IL-6 in AS. Therefore, we evaluated the effect of IL-6 on pTh17 cell activation, and it's mechanism, using ex vivo and mouse model of AS. As a result, we found that pTh17 cell is dependent on the cytokine milieu with IL-6. We confirmed pTh17 cells play a pathogenic role at sites of inflammation. As a mechanism, it was revealed that IL-6 induced STAT 3 phosphorylation contributes to the increased pTh17 responses in AS patients with peripheral arthritis. Though validation of our results is required, IL-6 inhibitor can be a promising treatment for inflammation in AS patients with peripheral arthritis.

T-cell immune response predicts the risk of critical SARS-Cov2 infection in hospitalized COVID-19 patients

IntroductionThis study aimed to identify markers of disease worsening in patients hospitalized for SARS-Cov2 infection. Patients and methodsPatients hospitalized for severe recent-onset (<1 week) SARS-Cov2 infection were prospectively included. The percentage of T-cell subsets and plasma IL-6 at admission (before any steroid therapy) were compared between patients who progressed to a critical infection and those who did not. ResultsThirty-seven patients (18 men, 19 women) were included; 11 (30%) progressed to critical infection. At admission, the critical infection patients were older (P = 0.021), had higher creatinine levels (P = 0.003), and decreased percentages of circulating B cells (P = 0.04), T cells (P = 0.009), and CD4+ T cells (P = 0.004) than those with a favorable course. Among T cell subsets, there was no significant difference between the two groups except for the percentage of Th17 cells, which was two-fold higher in patients who progressed to critical infection (P = 0.028). Plasma IL-6 at admission was also higher in this group (P = 0.018). In multivariate analysis, the percentage of circulating Th17 cells at admission was the only variable associated with higher risk of progression to critical SARS-Cov2 infection (P = 0.021). ConclusionThis study suggests that an elevated percentage of Th17 cells in patients hospitalized for SARS-Cov2 infection is associated with an increased risk of progression to critical disease. If these data are confirmed in a larger study, this marker could be used to better target the population of patients in whom tocilizumab could decrease the risk of progression to critical COVID-19.

Single-Cell Transcriptomics Reveals Peripheral Immune Responses in Anti-Synthetase Syndrome-Associated Interstitial Lung Disease.

ObjectiveInterstitial lung diseases (ILDs) secondary to anti-synthetase syndrome (ASS) greatly influence the prognoses of patients with ASS. Here we aimed to investigate the peripheral immune responses to understand the pathogenesis of this condition.MethodsWe performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from 5 patients with ASS-ILD and 3 healthy donors (HDs). Flow cytometry of PBMCs was performed to replenish the results of scRNA-seq.ResultsWe used scRNA-seq to depict a high-resolution visualization of cellular landscape in PBMCs from patients with ASS-ILD. Patients showed upregulated interferon responses among NK cells, monocytes, T cells, and B cells. And the ratio of effector memory CD8 T cells to naïve CD8 T cells was significantly higher in patients than that in HDs. Additionally, Th1, Th2, and Th17 cell differentiation signaling pathways were enriched in T cells. Flow cytometry analyses showed increased proportions of Th17 cells and Th2 cells, and decreased proportion of Th1 cells in patients with ASS-ILD when compared with HDs, evaluated by the expression patterns of chemokine receptors.ConclusionsThe scRNA-seq data analyses reveal that ASS-ILD is characterized by upregulated interferon responses, altered CD8 T cell homeostasis, and involvement of differentiation signaling pathways of CD4 T cells. The flow cytometry analyses show that the proportions of Th17 cells and Th2 cells are increased and the proportion of Th1 cells is decreased in patients with ASS-ILD. These findings may provide foundations of novel therapeutic targets for patients with this condition.

Interleukin17A: A Potential Target for Its Plausible Roles in the Pathogenesis of Idiopathic Epistaxis.

Introduction:It has been reported that inflammation may be a potential risk factor for the progression of epistaxis. Due to the major roles played by Th17 in the induction of inflammation, the present study aimed to assess the serum levels of Interleukin 17A (IL-17A) and IL-23, as the most important cytokines in the Th17 pathway, as well as IFN-, IL-4, and IL-10 serum levels, as regulatory cytokines for Th17 cells in patients with idiopathic epistaxis. Materials and Methods:The serum levels of IL-4, IL-10, IL-17A, IL-23, and IFN- were evaluated in 90 patients with idiopathic epistaxis and 90 healthy controls using enzyme-linked immunosorbent assay (ELISA) technique.Results:The obtained results pointed out that the serum levels of IL-17A and IL-10, but not IL-4 and IL-23, were significantly up-regulated, and IFN- serum levels were significantly down-regulated in patients with idiopathic epistaxis. Furthermore, female patients with epistaxis had higher IL-10 serum levels. Conclusions:As evidenced by the results of the present study, IL-17A is the main cytokine which participates in the pathogenesis of idiopathic epistaxis; moreover, in association with IL-10, it can be regarded as the suppressor of IFN- in patients.

Increased expression of T helper 17 cells and interleukin-17 in atopic dermatitis: a systematic review and meta-analysis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with genetic susceptibility and recurrent attacks. Research examining the etiology of this disease has mainly focused on environmental factors and immunity, with immune disorders believed to be the main factor in the occurrence and development of AD. While some studies have demonstrated that increased proportion of T helper 17 (Th17) cells in the lesions of specific dermatitis mouse models, the expression of Th17 cells and interleukin (IL)-17 in patients with AD remains controversial. Related literatures were retrieved from English databases including PubMed, Embase, and Ovid-Medline. Literatures published from the establishment of the database to April 2021 were identified using the following keywords: AD, T helper cell 17 (Th17 cell), and interleukin 17 (IL-17). Review Manager5.3 software was adopted for meta-analysis. A total of 8 studies, involving 1,147 subjects, related to the pathogenesis of AD were included in this meta-analysis. The analysis revealed that the expression of Th17 cells in patients with AD was higher than that in healthy patients (P<0.00001), and the serum expression of IL-17 was also elevated in patients with AD compared to healthy participants (P=0.0001). A total of 8 publications related to the pathogenesis of AD were analyzed. The meta-analysis found that patients with AD had higher expressions of Th17 cells and IL-17 compared to healthy subjects, suggesting that AD may be related to Th17 cells and IL-17.