Changes in type 2 innate lymphoid cells and serum cytokines in sublingual immunotherapy in pediatric patients with allergic rhinitis.

BACKGROUND: Type 2 innate lymphoid cells (ILC2) are upregulated in childhood allergic rhinitis (AR) and are associated with AR severity. This study aimed to investigate changes in the ILC2 milieu in pediatric patients with AR after sublingual immunotherapy (SLIT). METHODS: Forty- pediatric patients with AR received house dust mite (HDM) allergen extract for SLIT group and thirty pediatric patients received placebo in the study, respectively. The levels of ILC2, ILC2-related cytokines (IL-5/IL-13) and their transcription factors (GATA binding protein 3, retinoic acid-related orphan receptor α) in the circulation were assessed after 1- and 2-year SLIT. Moreover, peripheral blood mononuclear cells (PBMCs) in patients were prepared and stimulated by recombinant thymic stromal lymphopoietin, IL-25, and IL-33 after 2-year SLIT. Subsequently, the levels of ILC2, IL-5, and IL-13 were tested. RESULTS: The frequency of ILC2 and the levels of their transcription factors in the circulation were significantly decreased after SLIT in the SLIT group. The levels of ILC2-related cytokines in the SLIT group showed the same trend. The frequency of ILC2 was positively correlated with transcription factors and cytokines after SLIT. SLIT was observed to reduce the ability of HDM sensitization to generate the ILC2 milieu in PBMCs. CONCLUSIONS: Changes in the ILC2 milieu may be correlated with the curative effect and immune regulation function of SLIT. Our results suggested that the regulatory effect on ILC2 is part of the therapeutic mechanism of SLIT.

LncRNA JPX contributes to Treg/Th17 imbalance in allergic rhinitis via targeting the miR-378g/CCL5 axis.

Aim: T-regulatory (Treg)/T-helper (Th) 17 imbalance contributes to the pathogenesis of allergic rhinitis (AR). Long non-coding RNAs (lncRNAs) participate in the progression of AR. Herein, the effect of lncRNA JP X on Treg/Th17 balance in AR was explored.Methods: CD4+ T cells were isolated from patients with AR and healthy control. The percentage of Treg and Th17 cells were examined by flow cytometry. The levels of JP X, miR-378g, CCL5, T GF-ß, and IL-17A were tested using qRT-P CR. The protein expression of Foxp3 and RORγt was measured by western blot.Results: The data showed that an imbalance of Treg/Th17 was associated with AR. Upregulation of JP X was found in AR, and knockdown of which improved the imbalance of Treg/Th17. Furthermore, JP X functioned as a sponge of miR-378g to upregulate CCL5. Inhibition of miR-378g reversed the effects on Treg/Th17 induced by silencing of JP X. Moreover, overexpression of CCL5 reversed miR-378g-induced effects.Conclusion: In conclusion, depletion of JP X promoted Treg/Th17 balance in AR via regulating the miR-378g/CCL5 axis. The findings provided a novel therapeutic insight for AR.

Prevalence of allergic rhinitis comorbidity with asthma and asthma with allergic rhinitis in China: A meta-analysis.

BACKGROUND: Allergic rhinitis (AR) and asthma are the most common inflammatory diseases of the airways. The relationship between asthma and AR is widely and clinically recognised. The concept "one airway, one disease" has been gradually accepted. However, in China, we could not find any systematic review and meta-analysis on the prevalence of AR with asthma and asthma with AR. OBJECTIVE: The aim of this research was to carry out a meta-analysis on the results of all conducted studies to present valid information about the co-occurrence rate of AR with asthma and asthma with AR in China. METHODS: Pubmed/Medline, Science, Springer, Elsevier, Embase, Wanfang data, VIP, CBM, and CNKI were searched systemically and data were extracted from eligible studies by two independent reviewers. Meta-analysis, study quality assessment, and publication bias assessments were all done using Stata 12.1 software. RESULTS: The results of this meta-analysis showed that pooled prevalence estimates of AR with asthma ranged from 6.69% to 14.35%, asthma with AR from 26.67% to 54%. Furthermore, an overall prevalence of 10.17% (95% CI 9.08-11.27%) was ascertained for AR with asthma, and 38.97% (95% CI 34.42-43.53%) for asthma with AR. CONCLUSIONS: The present meta-analysis comprehensively provided the first quantitative summary of the prevalence of AR with asthma and asthma with AR in China. Our study demonstrated that, in China, asthma and AR are often comorbid diseases and co-exist in the same patients. There is a close correlation between AR and asthma from an epidemiological standpoint.

Knockdown of NFBD1/MDC1 enhances chemosensitivity to cisplatin or 5-fluorouracil in nasopharyngeal carcinoma CNE1 cells.

Nasopharyngeal carcinoma (NPC) is a rare but highly invasive cancer that is prevalent among people of southern Chinese ancestry in southern China and Southeast Asia. Radiotherapy and cisplatin (CDDP)-based chemotherapy are the main treatment options. Unfortunately, disease response to concurrent chemoradiotherapy varies among patients with NPC, and many cases are resistant to CDDP and radiotherapy. NFBD1 functions in cell cycle checkpoint activation and DNA repair following DNA damage. In this study, we identified the NFBD1 as a tractable molecular target to chemosensitize NPC cells. NFBD1 expression in NPC CNE1 cell lines was depleted using lentivirus-mediated short hairpin RNA, and the elevated sensitivity of these NFBD1-inhibited NPC cells to therapeutic reagent CDDP and 5-fluorouracil (5-FU) was evaluated using MTS assays. Flow cytometry analysis also showed that NFBD1 knockdown led to an obvious induction of apoptosis in CDDP- or 5-FU-treated CNE1 cells. Furthermore, we implicated the involvement of NFBD1 in Rad51 and DNA-PKcs foci formation following CDDP or 5-FU chemotherapy. In conclusion, NFBD1 knockdown improves the chemosensitivity of NPC cells by inhibiting cell growth and promoting apoptosis through the impairment of DNA damage repair, suggesting NFBD1 as a novel therapeutic target for NPC.

Genetic risk of TNFSF4 and FAM167A-BLK polymorphisms in children with asthma and allergic rhinitis in a Han Chinese population.

BACKGROUND: Asthma and allergic rhinitis (AR) frequently occur as comorbid diseases of the upper airways. Single-nucleotide polymorphisms (SNPs) in the TNFSF4 and FAM167A-BLK genes have recently been shown to be associated with various immune-related disorders. OBJECTIVE: Our aim was to determine whether TNFSF4 or FAM167A-BLK polymorphisms confer genetic susceptibility to asthma and AR in a Han Chinese population. METHODS: We performed a case-control study of 290 asthmatic children and 252 healthy controls. Nine SNPs in the TNFSF4 region (rs1234313, rs1234314, rs1234315, rsl 2039904, rs844648 and rsl 0912580) and the FAM167A-BLK region (rs2254546, rs13277113 and rs1600249) were detected using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: This study revealed that three SNPs in TNFSF4 (rsl 234313, rsl 234314 and rsl 234315) and two SNPs in FAM167A-BLK (rs2254546 and rsl 600249) were significantly correlated with asthma and AR, while SNP rsl600249 was associated with asthma without allergic rhinitis as a risk factor. Further, we demonstrated synergistic effects between the TNFSF4 and FAM167A-BLK SNPs. CONCLUSION: This study supports that the SNPs in TNFSF4 and FAM167A-BLK may be involved in asthma and AR gene risk in the Han Chinese cohort.

Association between JAK1 gene polymorphisms and susceptibility to allergic rhinitis.

OBJECTIVES: Allergic rhinitis (AR) is an inflammatory disorder of the upper airway. Janus kinase 1 (JAK1), a member of JAK family, has recently been found to participate in the immune response and the development of allergic airway disease. This study was performed to evaluate the potential association of JAK1 polymorphisms with AR in a Chinese Han population. METHODS: A case-control study was performed in 450 Chinese AR patients and 615 healthy controls. Three SNPs in the JAK1 gene, rs3790532, rs310241 and rs2780815, were analyzed using a polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP). RESULTS: An association was detected between SNP rs310241 in the JAK1 gene and AR in a Chinese Han population. However, no significant association was observed between the polymorphisms rs3790532 and rs2780815 and AR. For rs310241, the CC genotype and the C allele significantly increased the risk of AR. Furthermore, we found that the ACG haplotype in JAK1 gene was positively correlated with AR, while the GTG haplotype was associated with a significantly decreased risk of AR. CONCLUSION: This study indicates that the JAK1 rs310241 C-related genotype and allele are involved in AR susceptibility, making them potentially useful genetic biomarkers for AR susceptibility in the Chinese Han population.

Protocadherin20 Acts as a Tumor Suppressor Gene: Epigenetic Inactivation in Nasopharyngeal Carcinoma.

Genetic alterations of 13q21 (PCDH 8,9,17, and 20) are frequently observed in multiple tumors, suggesting the presence of critical tumor suppressor genes (TSGs). Protocadherin20 (PCDH20), located at 13q21.2, belongs to the δ1-protocadherins, which constitutes one of the largest subgroup within the adherin superfamily. Frequent downregulation/silencing of PCDH20 was found in NPC cell lines using semiquantitative PCR. PCDH20 mRNA was broadly expressed in normal nasopharyngeal tissues and cell lines. Promoter methylation of PCDH20 was observed in 80% (4/5) of NPC cell lines and 78.4% (40 of 51) of primary tumors by methylation-specific PCR, but rarely in normal nasopharygeal tissues and nasopharyngeal epithelial cell line (NP69). The silencing of PCDH20 can be reversed by pharmacological demethylation, indicating an epigenetic mechanism. Restoration of PCDH20 expression in NPC cells strongly suppressed cell numbers and colony formation. Overexpression of PCDH20 antagonized Wnt/ß-catenin signaling pathway and promoted ß-catenin to translocate from nucleus to cytoplasm and membrane. PCDH20 significantly inhibited the migration and invasion ability of NPC cells. PCDH20 also inhibited epithelial-mesenchymal transition (EMT) through enhanced expression of E-cadherin. Our study identified PCDH20 as a functional tumor suppressor and an important antagonist of Wnt/ß-catenin signaling and EMT, with frequent epigenetic inactivation in NPC.

MicroRNA expression profile of mature dendritic cell in chronic rhinosinusitis.

OBJECTIVE: Chronic rhinosinusitis (CRS), which includes CRS without nasal polyposis (CRSsNP) and with nasal polyposis (CRSwNP), shows imbalance of helper T cells (Th) and regulatory T cells (Treg). The balance of Th and Treg cells is orchestrated by dendritic cells (DCs). Recent studies show functions of DCs can be regulated by microRNAs (miRNAs or miRs). This study is aimed to investigate miRNAs expression profiles of peripheral blood DCs in CRS. METHODS: Peripheral blood samples of 30 patients with CRS and 7 patients with nasal septum deviation alone were collected. CD14(+) monocytes were isolated from these samples and differentiated into dendritic cells (DCs). Small RNAs were extracted from mature DCs and reversely transcribed into cDNA by Mir-XTM miRNA First-Strand synthesis method. MiRNA microarrays were used for miRNA expression analysis. Microarray results were validated by real-time PCR performed on five top list target genes. RESULTS: MiRNA microarrays showed that DCs from different types of patients have different sets of differential expressed miRNAs when comparing with Controls; they also share 31 commonly changed miRNAs among all three groups of CRS patients. Of these 31 miRNAs, 5 miRNAs were up-regulated and 25 miRNAs were down-regulated in all three types of CRS, while MiR-1290 was down-regulated in CRSsNP but up-regulated in both atopic CRSwNP and non-atopic CRSwNP. CONCLUSIONS: By comparing miRNA gene expression patterns in 3 types of CRS patients, we have been able to identify candidate miRNAs that might mediate the core pathogenesis of CRS through regulating dendritic cells. These miRNAs could serve as potential therapeutic targets for CRS.

Association study between interleukin-12 receptor ß1/ß2 genes and allergic rhinitis in the Chinese Han population.

Interleukin-12 (IL-12) plays a key role in the protection against allergic reaction induced by allergen as well as the differentiation of T helper 1 cells in patients with allergic rhinitis (AR), exerting its biological effects through binding to specific IL-12 receptors (IL-12Rs) termed IL-12Rß1 and IL-12Rß2. In this study, we investigated the relationship between polymorphisms in the IL-12R gene and AR in the Chinese Han population. A total of 543 patients with AR and 749 normal controls were genotyped for IL-12Rß1/rs438421, IL-12Rß2/rs3790565, rs3790567, and rs6679356 using a PCR restriction fragment length polymorphism analysis. The association study of each polymorphism of the IL-12Rß1 and IL-12Rß2 gene and AR showed that a significantly increased prevalence of the homozygous rs438421 GG genotype and G allele appeared in the AR patients compared with healthy controls. A significantly decreased prevalence of AG in rs438421 in AR patients is compared with healthy controls. Our research demonstrated an important association between polymorphisms in IL-12Rß1 and AR in the Chinese Han population. A strong association between rs438421 in a single nucleotide polymorphism of IL-12Rß1 and AR was identified.

High frequency of T helper type 9 cells in Chinese patients with allergic rhinitis.

BACKGROUND: T helper type 9 cells (Th9) are the most recently discovered subset of Th cells, and are involved in the pathology of several autoimmune and allergic diseases. The significance of Th9 cells in allergic rhinitis (AR) in Chinese patients is unclear. OBJECTIVE: The aim of this study was to investigate the possible role of Th9 cells in AR in Chinese patients. METHODS: Th9 cells and related factors were assessed by measuring levels of interleukin-9 (IL-9), PU.1, interferon-regulatory factor 4 (IRF4), and numbers of Th9 cells. A Th9-polarized milieu was evaluated by determining the levels of IL-4 and transforming growth factor-ß1 (TGF-ß1). Disease severity was assessed by rhino-conjunctivitis quality of life questionnaires (RQLQ), visual analog scale scores (VAS), and peripheral eosinophils (EOS) count. RESULTS: Levels of IL-4 and TGF-ß1 were elevated in AR groups versus healthy controls (P < 0.05). Levels of IL-9, PU.1, IRF4, and the numbers of Th9 cells were also significantly higher in the AR groups (P < 0.05). Furthermore, positive correlations were identified between IL-9 levels and EOS expression, RQLQ, and VAS scores (P < 0.01). CONCLUSIONS: Th9 cells and their relative factors were elevated in AR patients. Levels of Th9 polarization-related factors were much higher in AR patients, and the severity of disease was associated with a more severe Th9 response. These results suggest that AR patients present a favorable environment for Th9 differentiation, and that Th9 cells may play a crucial role in the pathology of AR in Chinese patients.

An aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress the Th17 response in allergic rhinitis patients.

A predominant Th17 population is a marker of allergic rhinitis (AR). The aryl hydrocarbon receptor (AhR) exhibits strong immunomodulation potential via regulation of the differentiation of T lymphocytes and dendritic cells (DCs) after activation by its ligand, such as 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). The aim of this study was to analyze the effect of AhR on Th17 differentiation by investigating the action of ITE on DCs and CD4(+) T cells from patients with AR. In all, 26 AR patients and 12 healthy controls were included in this study. The expression of interleukin (IL)-1ß, IL-6, IL-10, and IL-17 in the culture supernatant and the presence of Th17 cells in CD4(+) T cells and DC-CD4(+) T-cell co-culture system were measured before and after treatment with ITE. We show that ITE significantly induced cell secretion of IL-10 and inhibited IL-1ß and IL-6 production in DCs, and promoted IL-10 production and suppressed IL-17 expression in CD4(+) T cells in vitro. It also suppressed the expansion of Th17 cells in vitro. Our work demonstrates that ITE acts on DCs and CD4(+) T cells to inhibit the Th17 response that suppresses AR; the AhR-DC-Th17 axis may be an important pathway in the treatment of AR. ITE, a nontoxic AhR ligand, attenuated the Th17 response; thus, it appears to be a promising therapeutic candidate for suppressing the inflammatory responses associated with AR.

Allergen induced Treg response in the peripheral blood mononuclear cells (PBMCs) of patients with nasal polyposis.

BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disease of the nasal cavity and sinuses regulated by T cells. Regulatory T (Treg) cells are involved in controlling immune responses and inhibiting the allergen-specific effector cell response. The aim of this study was to evaluate whether NP patients had defects in Treg cells after specific allergen exposure and the possible correlation between atopy and Treg cells. METHODS: Peripheral blood mononuclear cells (PBMCs), isolated from NP patients and controls, were cultured with allergen+phytohemagglutinin (PHA) or PHA stimulation for 48h. The frequency of CD4+CD25+Foxp3+ cells was measured by flow cytometry. The level of Foxp3 was measured by Real-time PCR. Concentrations of Interferon-γ (IFN-γ), Interleukin-4 (IL-4), Interleukin-5 (IL-5), Interleukin-10 (IL-10) and transforming growth factor-ß (TGF-ß) in culture supernatants were determined by ELISA. RESULTS: Both atopic and non-atopic NP patients had a significantly decreased frequency of Treg cells and Foxp3 level in allergen stimulated PBMCs, also significantly decreased TGF-ß level in culture supernatants. The decrease was even more striking in the atopic group. Also, there were significantly negative correlations between Treg cells and IFN-γ, IL-4, IL-5. Moreover, inthe atopic group, allergen stimulation downregulated Treg cells and increased IFN-γ, IL-4, IL-5 levels, while upregulating Treg cells and decreasing IFN-γ, IL-4, IL-5 levels in controls. CONCLUSIONS: Patients with NP have a defective Treg cell response after allergen stimulation which is related to excessive Th1 and Th2 responses to specific allergens. Atopy may increase the impairment of Treg and exacerbate NP through the defective suppression of Treg on Th1 and Th2.

ANO1 as a marker of oral squamous cell carcinoma and silencing ANO1 suppresses migration of human SCC-25 cells.

OBJECTIVES: The purpose of this study is to confirm that ANO1 correlates with occurrence and metastasis of OSCC. STUDY DESIGN: Immunohistochemistry was used to detect the expression of ANO1 in 160 specimens of OSCC and normal tissues. Lentiviral silencing ANO1 was used in SCC-25 cell line to study the cell migration and cell detachment. RESULTS: Immunohistochemical staining revealed that ANO1 was expressed in a large majority (132 out of 160, 82.5%) of OSCC specimens and that the rate of ANO1 expression in OSCC was significantly higher than that of normal tissue (P<0.05); The rate of ANO1 expression was higher in metastatic tumors than in non-metastatic tumors, and the difference was significant (P<0.05). The results of cell migration assay showed that the percentage of cells through the membrane was 26.61 ±0.81 in assay group, and 54.26 ±3.74 in control group, respectively (t=-16.22,P<0.0001). The results of cell detachment assay showed that the percentage of cells detachment was 37.42 ±0.90 in assay group, and 87.38 ±1.59 in control group, respectively (t=-62.34, P<0.0001). The results of wound healing assay showed the assay group had a reduced migration rate compared with the control group in 32 h (F=1038.78, P<0.0001). Wound closure was no significantly different between the assay and control cells when DIDS was used in wound healing assay (F=4.61,P>0.05). CONCLUSIONS: Our study shows that abnormal expression of ANO1 correlated with the occurrence and metastasis of OSCC in clinical specimens and that silencing ANO1 greatly reduced migration ability of scc-25 cells. Calcium activated chloride channel activity of ANO1 promoted the cell migration. Thus, ANO1 could represent a new diagnostic biomarker and a potentially important therapeutic target of OSCC.

Comparative safety of monoclonal antibodies in chronic inflammatory airway diseases (chronic sinusitis with nasal polyposis and asthma): A network meta-analysis.

OBJECTIVE: Several monoclonal antibodies (MoAbs) targeting specific type 2 immune reactions have been developed as innovative therapeutic approaches for chronic inflammatory airway diseases, such as chronic sinusitis with nasal polyps (CRSwNP) and asthma. However, the clinical safety of these MoAbs and how to choose them are not clear. Therefore, we aimed to assess the systemic drug- and dose-based safety of MoAbs in chronic airway inflammation using network meta-analysis (NMA). METHODS: Electronic databases were systematically searched for relevant studies published in English between January 2009 and December 2022. Eligible studies must have clearly reported adverse events (AEs) among the MoAbs' safety data. RESULTS: 1). Regarding serious AEs, mepolizumab was significantly safer than placebo; in terms of permanent treatment discontinuation, reslizumab and dupilumab were significantly safer than benralizumab. 2). Regarding asthma worsening, dupilumab was associated with the best safety profile; was safer than dupilumab/300 mg/q2-4w. 3). In terms of injection-site reactions, dupilumab posed a higher risk than placebo; dupilumab/300 mg/qw posed a higher risk than dupilumab/300 mg/q2w and dupilumab/300 mg/q2-4w; lebrikizumab/250 mg/q4w posed a higher risk than lebrikizumab/37.5 mg/q4w; mepolizumab/100 mg/q4w posed a higher risk than mepolizumab/75 mg/q4w; benralizumab/30 mg/q4-8w posed a higher risk than benralizumab/20 mg/q4-8w. 4) In CRSwNP patients combined with asthma, the risks of experiencing AEs were not increased. CONCLUSION: Overall, biologics are safe and well tolerated in chronic inflammatory airway disease. This drug- and dose-based NMA provides further evidence on the different safety profiles of different emerging MoAbs. This information may help guide rational drug use and provide clinical recommendations for choosing MoAbs. TRIAL REGISTRATION: SYSTEMATIC REVIEW REGISTRATION (PROSPERO #CRD42023387610).

Transforming growth factor-ß1 promotes Treg commitment in nasal polyposis after intranasal steroid treatment.

BACKGROUND: A predominant Th17 population and impaired Treg function is the marker of nasal polyposis (NP) in Chinese patients. TGF-ß1, a multifunction cytokine, is a vital factor involved in inducing or restricting specific Th cell development. However, its role in NP has still not been well understood. METHODS: In a double-blind trial, 30 subjects were randomized into 2 groups (15 steroid-treated NP, 15 untreated NP), and 15 normal subjects were allocated as control group. We analyzed the expression of TGF-ß1, p-Smad2, p-STAT3, Smad7, SOCS3, IL-10, IL-17A, Foxp3, and RORc in the NP tissue of Chinese patients using mRNA and protein detection methods. RESULTS: TGF-ß1, p-Smad2, IL-10, SOCS3, and Foxp3 expression was higher in steroid-treated NP patients than in untreated NP patients. Conversely, expression of p-STAT3, Smad7, IL-17A, and RORc was higher in untreated NP patients than in steroid-treated NP patients, demonstrating that TGF-ß1 was more likely to contribute to Treg commitment in Chinese NP patients after intranasal steroid treatment. CONCLUSIONS: TGF-ß1 may be a signature Treg cytokine, which is valuable for obtaining a clear understanding of the pathogenesis of NP. Moreover, intranasal steroid treatment attenuated the chronic inflammatory response in these patients by promoting Smad-dependent Treg functions and reducing STAT3-mediated Th17 reactions.

Significance of the IL-6 pathway in nasal polyposis in Chinese patients.

BACKGROUND: The interleukin-6 (IL-6) pathway is known to be important in Th17 cell differentiation and in the pathology of many inflammatory disorders. However, the significance of the IL-6 pathway in nasal polyposis (NP) in Chinese patients remains unclear. OBJECTIVE: The aim of this study was to evaluate the functions of the IL-6 pathway in NP in Chinese patients. METHODS: The levels of IL-6 pathway components, including IL-6, soluble IL-6 receptor (sIL-6R), phosphoSTAT3 (pSTAT3), and suppressor of cytokine signalling 3 (SOCS3), were assessed. The Th17 milieu was examined by measuring the levels of retinoid acid-related orphan receptor C (RORc) and IL-17A. RESULTS: Levels of IL-6 pathway components, RORc, and IL-17A were significantly higher in both NP groups than in the control(p<0.05). Furthermore, significantly higher levels of pSTAT3, RORc, and IL-17A, and significantly lower levels of SOCS3 were found in the atopic group than in the non-atopic group(P<0.05). IL-6 and sIL-6R levels were not significantly different between the 2 NP groups(P>0.05). pSTAT3 exhibited significantly positive correlations with RORc and IL-17A(P<0.01). CONCLUSIONS: The expression levels of the IL-6 pathway components were significantly higher in NP patients. Moreover, p-STAT3 levels were much higher in the atopic group, and were associated with a more severe Th17 response. These results suggest that the IL-6 pathway may play a crucial role in the pathology of NP in Chinese patients, and atopy may contribute to NP by affecting the IL-6 pathway.

Anti-inflammatory Mechanisms of IL-38 in Chinese Patients with Allergic Rhinitis.

Background: T-helper 17 (Th17) cell response is engaged in the onset of allergic rhinitis (AR). Moreover, interleukin (IL)-38 is thought to be involved in inhibiting cytokine secretion in the Th17 pathway. Objective: To evaluate the regulatory function of IL-38 on abnormal Th17 responses in Chinese patients with AR. Methods: Forty-five participants, divided into an AR group (n=25) and a control group (n=20), were recruited for the study. In addition, the expression of IL-38 and Th17-related cytokines was measured as well as the Th17 cell count in participants. By implementing recombinant IL-38 (rIL-38), the intervention of human peripheral blood mononuclear cells (PBMCs) was performed. Then, flow cytometry, polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) were used to detect the Th17 milieu. Results: The expression of IL-38 in the AR group notably reduced compared with that in the control, whereas Th17 cell frequency and the expression levels of its transcription factor (RORC) and cytokines (IL-17A and IL-23) increased. The differentiation and immune function of Th17 cells in PBMCs were inhibited by rIL-38. Conclusion: Th17 responses are inhibited by IL-38 in patients with AR. Therefore, the obtained findings indicate that IL-38 is a potential therapeutic target for Chinese patients with AR.

Quercetin improves the imbalance of Th1/Th2 cells and Treg/Th17 cells to attenuate allergic rhinitis.

Allergic rhinitis (AR) is a common inflammation that affects many people globally. Quercetin has anti-allergic biological activity in AR. Here, we aimed to explore the effects of quercetin on type 1 helper T (Th1)/Th2 and regulatory T cells (Treg)/Th17 balance. We established an ovalbumin (OVA)-induced mouse model and orally administered 20, 35, and 50 mg/kg/day quercetin. The nasal symptoms of mice were observed. The immunoglobulin levels, Treg/Th17-related factors, and pro-inflammatory factors were examined by ELISA. The differentiated inflammation cells were visualized using the diff-quick staining assay. The nasal histopathology was evaluated using H&E, periodic acid Schiff (PAS), and Giemsa staining assay. The results showed that quercetin attenuated OVA-induced rubbing and sneezing. Quercetin reduced IgE, IgG1, histamine, and increased IgG2 in serum. The number of differentiated inflammation cells and goblet cells in tissues that elevated by OVA was reduced by quercetin. Moreover, OVA increased the Treg cell percentage, the levels of IL-17, TGF-ß, IL-6, TNF-α, and decreased Th17 cell percentage, IL-10 and FOXP3 levels, while quercetin abrogated their levels induced by OVA. Additionally, quercetin inactivated the NF-κB pathway. Taken together, quercetin attenuated AR symptoms by balancing the Th1/Th2, Treg/Th17 ratios, and inactivating the NF-κB pathway. The results suggested that quercetin may use for AR treatment.

Reciprocal roles of STAT3 and STAT5 in nasal polyposis.

PURPOSE: Nasal polyposis (NP) is a chronic inflammatory disease that is characterized by increased populations of Th17 cells and impairment of Treg cells function in Chinese patients. Recent studies have shown that signal transducer and activator of transcription 3 (STAT3) and STAT5 are indispensable in the development and maintenance of Th17 and Treg cells. We investigated the roles of STAT3 and STAT5 in the imbalance of Th17 and Treg cells in NP. MATERIALS AND METHODS: The levels of IL-6, IL-2, pSTAT3, pSTAT5, SOCS3, RORc, Foxp3, IL-17A, and TGF-ß1 were measured in patients with atopic NP, patients with nonatopic NP, and controls. We also evaluated the local distribution of Th17 and Treg cells by double immunofluorescence staining and the correlations between activated STAT3/STAT5 and Th17/Treg cell development were assessed. RESULTS: Increased levels of IL-6, pSTAT3, SCOS3, RORc, IL-17A, and CD4(+) RORc(+) cells, and decreased levels of IL-2, pSTAT5, Foxp3, TGF-ß1, and CD4(+) Foxp3(+) cells were detected in both NP groups compared to controls (P < .05). The differences in all expression levels (except for IL-6) were significant between atopic and nonatopic patients (P < .05). There was a positive correlation between pSTAT3/pSTAT5 levels and Th17/Treg development and a negative correlation between SOCS3 and pSTAT3 in NP (P < 0.01). CONCLUSIONS: The results suggest that STAT3 and STAT5 may function through the IL-6 and IL-2 pathways to play a role in the imbalance of Th17/Treg in NP. An even more exaggerated imbalance of Th17/Treg caused by atopy may be correlated to the improper ratio of activated STAT3/STAT5.

Survival analysis of laryngeal carcinoma without laryngectomy, radiotherapy, or chemotherapy.

This study aimed at investigating the survival rate and prognostic factors of laryngeal carcinoma patients in the absence of the use of laryngectomy, radiotherapy, and chemotherapy. A total of 167 cases of laryngeal carcinoma without the use of laryngectomy, radiotherapy, or chemotherapy were analyzed retrospectively. Surveyed items included age, smoking history, tumor family history, tuberculosis history, primary site, pathological grade, T-stage, N-stage, clinical stage, and whether tracheotomy had been performed. Survival rates were calculated using the Kaplan-Meier method. For univariate analysis, comparison among/between groups was performed using the log-rank test. Multivariate analysis was carried out using the Cox proportional hazard model. Overall median survival time was 16 ± 1.44 months, and overall 1- and 2-year survival rates were 56.4 and 26.5%, respectively. No patient survived over 5 years in cases diagnosed for more than 5 years (except for cases that were lost). The median survival time of clinical stage 0/I/II was 28 ± 3.81 months, and 1- and 2-year survival rates were 79.3 and 59.3%, respectively; the median survival time of III/IV clinical stages was 11 ± 1.32 months, and 1- and 2-year survival rates were 45.5 and 10.6%, respectively. Univariate analysis showed that primary site, pathological grade, T-stage, N-stage, and clinical stage were significant prognostic factors for the survival of the patients (P < 0.05). Whether tracheotomy had been performed was not significant for affecting survival rates. Multivariate analysis showed survival rates were statistically correlated with T-stage and N-stage (P < 0.05). The development of laryngeal carcinoma course was faster, without treatment to the tumor itself, even if palliative surgery such as tracheostomy would not improve the survival rate. In laryngeal carcinoma patients with no surgery, radiotherapy or chemotherapy, the factors affecting the survival rates include primary site, pathological grade, T-stage, N-stage, and clinical stage, and of them, T-stage and N-stage are the independent prognostic factors.