Th17 Cells In Blood Research Articles

Retracted: Clinical Significance of Peripheral Blood Th1 and Th17 Cell Content and Serum IL-35 and IL-17 Expression in Patients with Ankylosing Spondylitis.

[This retracts the article DOI: 10.1155/2022/6540557.].

003 Interleukin (IL)-26 drives pathogenic IL-17A responses through a TH17-keratinocyte crosstalk

Interleukin (IL)-26 is a TH17 cytokine with known antimicrobial and pro-inflammatory functions and is highly expressed in tissues of TH17-mediated inflammatory diseases including psoriasis. However, the expression of IL-26 with respect to IL-17A and its precise function in the context of pathogenic TH17 responses are still unclear. In this study, we used flow cytometry-based fluorescent in situ hybridization of blood TH17 cells along with single-cell and spatial transcriptomics of psoriatic skin lesions to analyze the dynamic of the regulation of IL-26 expression in TH17 cells. We show that blood TH17 cells contain a large population of IL-26-producing cells that do not produce IL-17A. Unlike IL-17A-producing cells, these IL-26-producing cells develop at early stages of TH17 differentiation and do not require TGF-β. However, when exposed to TGF-β, IL-26-producing cells transition into IL-17 producers, a process also observed in psoriatic skin lesions, where TGF-β is highly expressed by basal keratinocytes in close vicinity to IL-26-producing T cells. T cell-derived IL-26 was able to induce TGF-β expression in keratinocytes themselves, suggesting a mechanism by which TH17 cells control IL-17A responses in tissues via the expression of IL-26. Thus, our study identifies IL-26-producing cells as an early differentiation stage of TH17 cells that can further differentiate into IL-17A producing cells upon tissues infiltration via a paracrine loop involving TGF-β.

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.

Dual activation of estrogen receptor alpha and glucocorticoid receptor upregulate CRTh2-mediated type 2 inflammation; mechanism driving asthma severity in women?

Type 2-high asthma is characterized by elevated levels of circulating Th2 cells and eosinophils, cells that express chemoattractant-homologous receptor expressed on Th2 cells (CRTh2). Severe asthma is more common in women than men; however, the underlying mechanism(s) remain elusive. Here we examined whether the relationship between severe asthma and type 2 inflammation differs by sex and if estrogen influences Th2 cell response to glucocorticoid (GC). Type 2 inflammation and the proportion of blood Th2 cells (CD4+ CRTh2+ ) were assessed in whole blood from subjects with asthma (n=66). The effects of GC and estrogen receptor alpha (ERα) agonist on in vitro differentiated Th2 cells were examined. Expression of CRTh2, type 2 cytokines and degree of apoptosis (Annexin V+ , 7-AAD) were determined by flow cytometry, qRT-PCR, western blot and ELISA. In severe asthma, the proportion of circulating Th2 cells and hospitalizations were higher in women than men. Women with severe asthma also had more Th2 cells and serum IL-13 than women with mild/moderate asthma. Th2 cells, eosinophils and CRTh2 mRNA correlated with clinical characteristics associated with asthma control in women but not men. In vitro, GC and ERα agonist treated Th2 cells exhibited less apoptosis, more CRTh2 as well as IL-5 and IL-13 following CRTh2 activation than Th2 cells treated with GC alone. Women with severe asthma had higher levels of circulating Th2 cells than men, which may be due to estrogen modifying the effects of GC, enhancing Th2 cell survival and type 2 cytokine production.

Ephedrae Herba polysaccharides inhibit the inflammation of ovalbumin induced asthma by regulating Th1/Th2 and Th17/Treg cell immune imbalance

AimsThis study aimed to investigate the anti-asthma effects of Ephedrae Herba polysaccharides (PE) and possible mechanisms related to immune inflammatory response. MethodsAn asthma model was established in rats using ovalbumin (OVA). Seventy rats were randomly assigned to five groups: control, model, dexamethasone (DEX, 0.075 mg/kg), low dose polysaccharides (LPE, 137.71 mg/kg) and high dose polysaccharides (HPE, 275.42 mg/kg). The cough and asthma were used to evaluate the basic state of asthmatic rats. Histological studies were evaluated by hematoxylin and eosin (H&E), Masson, and periodic acid-schiff (PAS) staining. The levels of interferon-γ (IFN-γ), interleukin (IL)-4, immunoglobulin E (IgE), tumor necrosis factor α (TNF-α), and IL-17A in bronchoalveolar lavage fluid (BALF), and the levels of transforming growth factor β1 (TGF-β1), IL-6, and IL-10 in serum were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA levels of Ifn-γ, Il-4, Tgf-β1, Il-6, Il-10, Tnf-α, Il-13, and Il-17a were evaluated by quantitative real-time reverse transcription (qRT)-PCR. The dendritic cell (DCs), T helper cell (Th), natural killer cell (NK), regulatory T cell (Treg), and Th17 cells in blood, the lymphocytes, macrophages and neutrophils in spleen, and cell apoptosis and reactive oxygen species (ROS) in lung were analysed by flow cytometry (FCM). Immunohistochemistry (IHC) was used to stain DCs (CD11c+, CD86+, and CD80+), macrophages (CD68+), and neutrophils (MPO+) in the spleen and lung. The protein levels of IL-17A, CD11c, CD86, and CD80 in lung were measured by western blot. ResultsOur study demonstrated that PE could effectively improve the symptoms of asthmatic rats, ameliorate the lung pathological injury, inhibit inflammation, apoptosis and oxidative stress, regulate the levels of macrophages, neutrophils, DCs, NK, Thc, Treg and Th17 cells. ConclusionPE could collectively inhibit the inflammation, apoptosis and ROS in asthma rats induced by OVA via regulating Th1/Th2 and Th17/Treg cell immune imbalance.

Correlation of acetyl-coenzyme A carboxylase 1 with Th17 and Th1 cells, serving as a potential prognostic biomarker for acute ischemic stroke patients.

BackgroundAcetyl‐coenzyme A carboxylase 1 (ACC1) regulates lipid homeostasis, T helper (Th) cell differentiation, oxidative stress, inflammation response, and neurological process, engaging in acute ischemic stroke (AIS) pathogenesis, while its clinical utility in AIS is unclear. Hence, this study intended to explore the correlation among blood ACC1, Th17, and Th1 cells, and ACC1’s potency as a prognostic biomarker for AIS management.MethodsACC1 in peripheral blood mononuclear cells (PBMCs) of 160 AIS patients and 30 controls were determined using RT‐qPCR; blood Th17 and Th1 cells in AIS patients were quantified by flow cytometry.ResultsACC1 was increased in AIS patients compared with controls (median (interquartile range): 2.540 (1.753–3.548) vs. 0.980 (0.655–1.743), p < 0.001), which exhibited a good value to reflect AIS risk with the area under the curve of 0.872 (95% CI: 0.805–0.939). Moreover, ACC1 was positively linked with Th17 (r = 0.374, p < 0.001) and Th1 (r = 0.178, p = 0.024) cells in AIS patients. Additionally, ACC1 (r = 0.328, p < 0.001), Th17 (r = 0.272, p = 0.001), and Th1 cells (r = 0.195, p = 0.014) were positively associated with the National Institutes of Health Stroke Scale score in AIS patients. ACC1 high vs. low (p = 0.038) and Th17 high vs. low (p = 0.026) were related to shortened recurrence‐free survival (RFS) in AIS patients, while Th1 cells (p = 0.179) were not correlated with RFS. Whereas ACC1 (p = 0.248), Th17 (p = 0.079), and Th1 cells (p = 0.130) were not linked with overall survival (OS) in AIS patients.ConclusionCirculating ACC1 overexpression correlates with increased Th17, Th1 cells, NIHSS score, and shortened RFS in AIS patients.

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.

Low SOCS3 expression in CD4+ T cells from pemphigus vulgaris patients enhanced Th1- and Th17-cell differentiation and exacerbated acantholysis via STAT activation

ObjectivePemphigus vulgaris (PV) is a chronic inflammatory autoimmune blistering disease. Aberrant SOCS3/STAT pathway activation is associated with many autoimmune diseases. This study explored the relationship between activation of the SOCS3/STAT pathway and abnormally increased proportions of Th1 and Th17 cells in the peripheral blood of PV patients as well as the effect of CD4+ T cells with abnormal SOCS3/STAT pathway activation on acantholysis. MethodsIn PV patients, the proportions of Th1 and Th17 cells in peripheral blood, the levels of IFN-γ and IL-17 in serum and the mRNA levels of SOCS3 and STAT1/3 in CD4+ T cells were detected. Then, SOCS3-knockdown primary CD4+ T cells were prepared, and cocultured with HaCaT cells. Finally, after SOCS3 knockdown and coculture, CD4+ T cells were collected, and the proportions of Th1 and Th17 cells, the protein levels of STAT1/3 and p-STAT1/3, and the levels of IFN-γ and IL-17 were measured. After 2 days of coculture, HaCaT cells were collected, inflammatory factors mRNA expression and acantholysis were assessed. ResultsIn PV patients, the proportions of Th1 (P = 0.016) and Th17 (P = 0.045) cells and the levels of IFN-γ (P = 0.010) were significantly increased. SOCS3 mRNA in CD4+ T cells was significantly decreased (P = 0.008), whereas STAT1 (P = 0.043) and STAT3 (P = 0.004) mRNA were significantly increased. After SOCS3 knockdown, the proportions of Th1 (P < 0.001) and Th17 (P = 0.006) cells, the levels of IFN-γ (P < 0.001) and IL-17 (P = 0.001), and the protein levels of p-STAT1 (P = 0.001) and p-STAT3 (P = 0.003) were significantly increased in the CD4+ T-shSOCS3–1 group. In the coculture system, the proportions of Th1 (P < 0.001) and Th17 (P < 0.001) cells, the levels of IFN-γ (P < 0.001) and IL-17 (P < 0.001), and the number of cell fragments (P < 0.001) were significantly increased in the CD4+ T-shSOCS3–1+HaCaT-PV-IgG group, whereas the protein level of desmoglein3 (Dsg3) was significantly decreased. In addition, PV-IgG significantly increased IFN-γ and IL-6 mRNA in HaCaT cells. ConclusionLow SOCS3 expression in CD4+ T cells from PV patients leads to overactivation of STAT, which causes CD4+ T cells to overdifferentiate into Th1 and Th17 cells. Additionally, PV-IgG-induced local inflammation in skin lesions, which is mediated by IFN-γ and IL-6, can aggravate this phenomenon. Furthermore, low SOCS3 expression in CD4+ T cells further exacerbates PV-IgG-induced acantholysis. Therefore, upregulating the expression of SOCS3 in CD4+ T cells of PV patients and maintaining the balance of the IFN-γ/STAT1/SOCS3 and IL-6/STAT3/SOCS3 pathways can alleviate acantholysis in patients with PV.

Relation of CDC42, Th1, Th2, and Th17 cells with cognitive function decline in Alzheimer's disease.

ObjectiveCell division cycle 42 (CDC42) regulates neurite outgrowth, neurotransmitter, and T help (Th) cell‐mediated neuroinflammation, while its clinical implication in Alzheimer's disease (AD) is not clear. The present study aimed to investigate the correlation of CDC42 with Th1, Th2, and Th17 cells, as well as CDC42’ longitudinal change and relation to cognitive function decline in AD patients.Methods150 AD patients were enrolled, then their blood Th1, Th2, and Th17 cells were quantified by flow cytometry at baseline; CDC42 was detected by RT‐qPCR and MMSE score was assessed at baseline and during 3‐year follow‐up. Meanwhile, CDC42, Th1, Th2, and Th17 cells were quantified in 30 Parkinson's disease (PD) patients and 30 healthy controls (HCs).ResultsCDC42 (p < 0.001) and Th2 cells (p < 0.001) were lowest in AD patients, followed by PD patients, highest in HCs; but Th1 cells (p = 0.001) and Th17 cells (p < 0.001) showed opposite trends. CDC42 was not related to Th1 cells (p = 0.134), positively correlated with Th2 cells (p = 0.023) and MMSE (p < 0.001), while negatively associated with Th17 cells (p < 0.001) in AD patients. CDC42 was only related to Th17 cells (p = 0.048) and MMSE (p = 0.048) in PD patients; and it was not linked with Th1, Th2, Th17 cells, or MMSE in HCs (all p > 0.05). During a 3‐year follow‐up, CDC42 was gradually declined in AD patients (p < 0.001), its decline was positively correlated with MMSE decline at 1 year (p = 0.004), 2 years (p = 0.005), and 3 years (p = 0.026).InterpretationCDC42 might have the potency to serve as a biomarker for estimating AD risk and progression.

Glaesserella parasuis induces IL-17 production might through PKC-ERK/MAPK and IκB/NF-κB signaling pathways

In our previous study, the outer membrane protein P2 of Glaesserella parasuis (G. parasuis) induced the production of interleukin-17A (IL-17A) in host cells. However, how the G. parasuis infection produces IL-17A in the host is unknown. In this study, at 48 hpi in piglets, the proportion of Th17 cells in the peripheral blood significantly increased as determined by flow cytometry, but the overall proportion was low. IL-17 mRNA and protein levels significantly increased in the lungs and spleens of infected piglets. Histopathological examination staining, immunohistochemistry and viability counts, revealed that IL-17 expression might be positively correlated with bacterial content and the degree of pathological injury in lung and spleen tissues. Furthermore, when infected with the G. parasuis Nagasaki strain compared with avirulent strain C5, the primary porcine alveolar macrophages (PAMs) significantly produced IL-17 in a time-dose dependent manner. In addition, we demonstrated that PKC, MEK and NF-κB signaling pathways were essential for G. parasuis-induced IL-17 production because the addition of corresponding inhibitors dramatically reduced IL-17 mRNA production. The phosphorylation levels of PKC, ERK1/2 and IκB in G. parasuis-infected primary PAMs also increased significantly as the infection dose increased as assessed by western blotting. Thus, these finding imply that IL-17 induced by G. parasuis infection is dependent on activation of PKC-ERK/MAPK and IκB/NF-κB signaling pathways.

MALT1 regulates Th2 and Th17 differentiation via NF-κB and JNK pathways, as well as correlates with disease activity and treatment outcome in rheumatoid arthritis

ObjectiveMALT1 regulates immunity and inflammation in multiple ways, while its role in rheumatoid arthritis (RA) is obscure. This study aimed to investigate the relationship of MALT1 with disease features, treatment outcome, as well as its effect on Th1/2/17 cell differentiation and underlying molecule mechanism in RA.MethodsTotally 147 RA patients were enrolled. Then their blood Th1, Th2, and Th17 cells were detected by flow cytometry. Besides, PBMC MALT1 expression was detected before treatment (baseline), at week (W) 6, W12, and W24. PBMC MALT1 in 30 osteoarthritis patients and 30 health controls were also detected. Then, blood CD4+ T cells were isolated from RA patients, followed by MALT1 overexpression or knockdown lentivirus transfection and Th1/2/17 polarization assay. In addition, IMD 0354 (NF-κB antagonist) and SP600125 (JNK antagonist) were also added to treat CD4+ T cells.ResultsMALT1 was increased in RA patients compared to osteoarthritis patients and healthy controls. Meanwhile, MALT1 positively related to CRP, ESR, DAS28 score, Th17 cells, negatively linked with Th2 cells, but did not link with other features or Th1 cells in RA patients. Notably, MALT1 decreased longitudinally during treatment, whose decrement correlated with RA treatment outcome (treatment response, low disease activity, or disease remission). In addition, MALT1 overexpression promoted Th17 differentiation, inhibited Th2 differentiation, less affected Th1 differentiation, activated NF-κB and JNK pathways in RA CD4+ T cells; while MALT1 knockdown exhibited the opposite effect. Besides, IMD 0354 and SP600125 addition attenuated MALT1’s effect on Th2 and Th17 differentiation.ConclusionMALT1 regulates Th2 and Th17 differentiation via NF-κB and JNK pathways, as well as correlates with disease activity and treatment outcome in RA.

Blood Th17 cells and IL-17A as candidate biomarkers estimating the progression of cognitive impairment in stroke patients.

BackgroundT helper (Th) cells regulate immunity and inflammation to engage in cognitive impairment in several neurological diseases, while their clinical relevance in stroke patients is not clear. The current study intended to assess the relationship of Th1 cells, Th17 cells, interferon‐gamma (IFN‐γ), and interleukin (IL)‐17A with cognitive function in stroke patients.MethodsOne hundred twenty stroke patients and 40 controls were enrolled in this muticenter study. Th1 and Th17 cells in peripheral blood were assessed by flow cytometry; meanwhile, IFN‐γ and IL‐17A in serum were detected by enzyme‐linked immunosorbent assay. Cognitive function of stroke patients was evaluated by Mini‐Mental State Examination (MMSE) score at enrollment (baseline), year 1, year 2, and year 3.ResultsTh1 cells (p = 0.037) and IFN‐γ (p = 0.048) were slightly increased, while Th17 cells (p < 0.001) and IL‐17A (p < 0.001) were greatly elevated in stroke patients compared with controls. Th17 cells (r s = −0.374, p < 0.001) and IL‐17A (r s = −0.267, p = 0.003) were negatively correlated with MMSE score at baseline, but Th1 cells and IFN‐γ were not. Meanwhile, Th17 cells (p = 0.001) and IL‐17A (p = 0.024) were increased in patients with cognitive impairment compared to those without cognitive impairment. Notably, Th17 cells were positively associated with 1‐year (r s = 0.331, p < 0.001), 2‐year (r s = 0.261, p = 0.006), and 3‐year (r s = 0.256, p = 0.011) MMSE decline; IL‐17A was positively correlated with 1‐year (r s = 0.262, p = 0.005), 2‐year (r s = 0.193, p = 0.045), but not 3‐year MMSE decline. However, both Th1 cells and IFN‐γ were not linked with MMSE decline.ConclusionTh17 cells and IL‐17A estimate the progression of cognitive impairment in stroke patients.

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.

T helper cell subsets and related target cells in acute COVID-19

Current review presents a brief overview of the immune system dysregulation during acute COVID-19 and illustrates the main alterations in peripheral blood CD4+ T-cell (Th) subsets as well as related target cells. Effects of dendritic cell dysfunction induced by SARS-CoV-2 exhibited decreased expression of cell-surface HLA-DR, CCR7 as well as co-stimulatory molecules CD80 and CD86, suggesting reduced antigen presentation, migratory and activation capacities of peripheral blood dendritic cells. SARS-CoV-2-specific Th cells could be detected as early as days 24 post-symptom onset, whereas the prolonged lack of SARS-CoV-2-specific Th cells was associated with severe and/or poor COVID-19 outcome. Firstly, in acute COVID-19 the frequency of Th1 cell was comparable with control levels, but several studies have reported about upregulated inhibitory immune checkpoint receptors and exhaustion-associated molecules (TIM3, PD-1, BTLA, TIGIT etc.) on circulating CD8+ T-cells and NK-cells, whereas the macrophage count was increased in bronchoalveolar lavage (BAL) samples. Next, type 2 immune responses are mediated mainly by Th2 cells, and several studies have revealed a skewing towards dominance of Th2 cell subset in peripheral blood samples from patients with acute COVID-19. Furthermore, the decrease of circulating main Th2 target cells basophiles and eosinophils were associated with severe COVID-19, whereas the lung tissue was enriched with mast cells and relevant mediators released during degranulation. Moreover, the frequency of peripheral blood Th17 cells was closely linked to COVID-19 severity, so that low level of Th17 cells was observed in patients with severe COVID-19, but in BAL the relative number of Th17 cells as well as the concentrations of relevant effector cytokines were dramatically increased. It was shown that severe COVID-19 patients vs. healthy control had higher relative numbers of neutrophils if compared, and the majority of patients with COVID-19 had increased frequency and absolute number of immature neutrophils with altered ROS production. Finally, the frequency of Tfh cells was decreased during acute COVID-19 infection. Elevated count of activated Tfh were found as well as the alterations in Tfh cell subsets characterized by decreased regulatory Tfh1 cell and increased pro-inflammatory Tfh2 as well as Tfh17 cell subsets were revealed. Descriptions of peripheral blood B cells during an acute SARS-CoV-2 infection werev reported as relative B cell lymphopenia with decreased frequency of nave and memory B cell subsets, as well as increased level of CD27hiCD38hiCD24 plasma cell precursors and atypical CD21low B cells. Thus, the emerging evidence suggests that functional alterations occur in all Th cell subsets being linked with loss-of-functions of main Th cell subsets target cells. Furthermore, recovered individuals could suffer from long-term immune dysregulation and other persistent symptoms lasting for many months even after SARS-CoV-2 elimination, a condition referred to as post-acute COVID-19 syndrome.

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.

Blood T-helper 17 cells and interleukin-17A correlate with the elevated risk of postpartum depression and anxiety.

BackgroundT‐helper (Th) cells regulate inflammation and immunity, which is implicated in psychological disorders. The current study aimed to explore the clinical role of blood Th1, Th2, and Th17 cells and their main secreted cytokines in postpartum depression (PPD) and postpartum anxiety (PPA).MethodsA total of 226 postpartum women were included. At 6 weeks postpartum, Edinburgh Postnatal Depression Scale (EPDS) and State Trait Anxiety Inventory 6 item version (STAI6) scores were assessed; meanwhile, blood Th1, Th2, and Th17 cells were detected by flow cytometry, serum interferon‐gamma (IFN‐γ), interleukin‐4 (IL‐4), and IL‐17A were detected by enzyme‐linked immunosorbent assay.ResultsThe incidence of PPD and PPA were 24.3% and 27.9%, respectively. Th17 cells and IL‐17A were positively correlated with EPDS score and STAI6 score (all p < 0.001). Besides, Th17 cells (p < 0.001) and IL‐17A (p = 0.002) were increased in PPD cases vs. non‐PPD cases, and they were also elevated in PPA cases vs. non‐PPA cases (both p < 0.05). However, Th1 cells, Th2 cells, IFN‐γ, and IL‐4 were not linked with EPDS score or STAI6 score (all p > 0.05); besides, they did not vary in PPD cases vs. non‐PPD cases or in PPA cases vs. non‐PPA cases (all p > 0.05). Multivariate logistic regression model analysis showed that Th17 cells were independently associated with an elevated risk of PPD (odds ratio [OR] = 1.600, p = 0.001) and PPA (OR = 1.371, p = 0.022).ConclusionBlood Th17 cells and IL‐17A are positively linked with the risk of PPD and PPA, indicating which may be involved in the development of PPD and PPA.

Clinical Significance of Peripheral Blood Th1 and Th17 Cell Content and Serum IL-35 and IL-17 Expression in Patients with Ankylosing Spondylitis.

Objective To evaluate the clinical significance of peripheral blood T helper cell 1 (Th1) and T helper cell 17 (Th17) cell content and serum (interleukin) IL-35 and IL-17 expression in patients with ankylosing spondylitis (AS). Methods In this retrospective study, we included and assigned 60 cases of AS patients enrolled in our hospital from January 2019 to January 2020 to an active group (ankylosing spondylitis disease activity score (ASDAS) ≥2.1, n = 28) and a static group (ASDAS<2.1, n = 32) according to the degree of disease activity. The logistic propensity score matching method was used to include 60 healthy individuals after a physical examination during the same period in the control group. The peripheral blood Th1 and Th17 cell content and the levels of serum IL-35 and IL-17 were determined and analyzed. Results Statistically significant differences were found in the Th1 cell ratio and Th17 cell ratio between the control group and the other two groups (P < 0.05), and the static group yielded a higher Th1 cell ratio and a lower Th17 cell ratio than the active group (P < 0.05). Statistically significant differences were also observed in the serum IL-35 and IL-17 levels between the control group and the other two groups (P < 0.05), and the static group had a higher IL-35 level and a lower IL-17 level than the active group (P < 0.05). Conclusion The imbalance of Th17/Th1 cell content of AS patients is characterized by high expression of IL-17 and low expression of IL-35. The increased activity of AS was associated with a dominant state of Th17 cells and a significant increase in IL-17 expression, indicating that Treg/Th17 imbalance is closely related to the development of AS, which may provide new ideas for the prevention and treatment of AS.

Wenyang Huazhuo Tuihuang Formula Inhibits the Th17/Treg Cell Imbalance and Protects against Acute-on-Chronic Liver Failure.

Objective Acute-on-chronic liver failure (ACLF) is a group of chronic liver diseases and caused by acute internal and external liver injury. Wenyang Huazhuo Tuihuang (WYHZTH) formula had a good clinical effect on promoting the resolution of jaundice. The aim of this study is to further investigate the mechanism of the WYHZTH formula in the ACLF rat model. Methods The ACLF rat model was constructed by combining human serum albumin with LPS and D-gal. WYHZTH was used to intervene and treat. The cytokines IL-17, IL-23, IL-10, and TGF-β were detected by ELISA and fluorescence-quantitative PCR. Flow cytometry was used to detect the percentage of Th17 and Treg cells in the peripheral blood and liver tissues of each group of rats. The pathological changes in the liver tissue were detected by hematoxylin-eosin staining, immunohistochemistry, and electron microscopy. Results Compared with the ACLF group, the WYHZTH formula and Thy significantly decreased the levels of ALT, AST, and CHE in the ACLF group. After drug intervention, apoptosis was significantly reduced. The PCNA expression decreased in the ACLF model group but increased in the WYHZTH or Thy group. Under transmission electron microscope, hepatocytes in the ACLF group showed obvious necrosis. After drug intervention, hepatocyte necrosis was reduced with most of the structure returning to normal. Conclusion This present study demonstrated that WYHZTH formula may protect against acute-on-chronic liver failure, which may be related to the inhibition of Th17/Treg cell imbalance.

Role of Oxidative Stress in Vascular Low-Grade Inflammation Initiation Due to Acute Salt Loading in Young Healthy Individuals.

This study aimed to investigate the effect of 7-day high-salt (HS) and the specific role of oxidative stress on vascular low-grade inflammation initiation in young salt-resistant healthy individuals. 30 young healthy individuals adhered to a 7-day low-salt (LS) diet (3.5 g salt/day), followed by a 7-day high-salt (HS) diet (~14.7 g salt/day) protocol. Pro- and anti-inflammatory cytokines, frequencies of peripheral blood Th17 and Treg cells, Th17/Treg ratio, enzymes SGK1, and p38/MAP kinase, as well as biomarkers of endothelial activation and oxidative stress, were measured before and after the 7-day HS diet protocol. Short-term HS diet significantly increased serum level of pro-inflammatory cytokines INF-γ, TNF-α, IL-9, and IL-17A levels, but also of anti-inflammatory cytokines IL-10 and TGF-β1. Relative amount of total SGK1 significantly increased, following the 7-day HS diet. Increased oxidative stress level, following HS diet, was negatively associated with the frequency of Treg cells. The increase in relative amount of total SGK1 in peripheral mononuclear cells following 7-day HS diet suggests lymphocyte (re)activation, in response to HS intake, resulting in enhanced production of pro-inflammatory (IL-17, INF-γ), but also anti-inflammatory cytokines (IL-10 and TGF-β1). Increased oxidative stress, due to HS loading, alters immune regulatory mechanisms, presumably via effects on Treg cells.

Th17/Treg cell balance in stable liver transplant recipients

BackgroundImmune monitoring of transplanted patients may provide a reliable basis for the individualization of immunosuppressive therapy. In addition, it might be applied for realizing the early and non-invasive diagnosis of acute allograft rejection. MethodsPercentages of TCD4 + IL-17+ (Th17) and TCD4 + CD25 + CD127dim/− (Treg) cells, as well as serum levels of interleukin (IL)-17 and transforming growth factor (TGF)-β1, were evaluated in 30 stable patients using flow cytometry and ELISA techniques before and six months after liver transplantation. Besides, the same cells and cytokines were quantified in 10 recipients with acute allograft rejection. ResultsSix months post-transplant, the percentage of Th17 and Treg cells in the peripheral blood of stable liver transplant recipients reduced significantly, but the Th17/Treg ratios were comparable to the pre-transplant period (1.24 vs. 1.56); however, Th17/Treg ratios in the rejection group was significantly higher than in the stable recipients (4.06 vs. 1.56, P-value = 0.001). Stable patients showed decreased amounts of serum IL-17 which was remarkably lower than in the rejection group (P-value = 0.01). Moreover, there was a significant correlation between the serum level of IL-17 and the percentage of Th17 cells (P-value <0.001). Th17 frequency was negatively associated with the liver allograft function. Notably, TGF-β1 levels differed neither between pre-and post-transplant samplings nor between stable and rejection groups. ConclusionSix months after liver transplantation, the mean Th17/Treg ratio in stable recipients remained comparable to the pre-transplant values; however, it was significantly elevated in patients with acute allograft rejection, suggesting the Th17/Treg ratio as a probable predictor of acute rejection.