European cytokine network最新文献

{"title":"Thymic stromal lymphopoietin suppresses markers of neuroinflammation and the JAK2/STAT5 pathway in activated microglia.","authors":"Qiao Zhou, Nanxue Cui, Shihai Zhang, Miaomiao Zhou, Younian Xu","doi":"10.1684/ecn.2023.0487","DOIUrl":"10.1684/ecn.2023.0487","url":null,"abstract":"<p><p>Thymic stromal lymphopoietin (TSLP) is highly expressed in the central nervous system in response to inflammation, but its exact function remains unclear. In this study, we used a model of LPS-stimulated microglia to investigate the direct impact of TSLP on microglial activation and the underlying mechanism. We measured oxidative stress, expression of microglial activation markers, and inflammatory indexes. The results show that TSLP treatment increased the expression of TSLP receptors and reduced LPS-induced oxidative stress, inflammation, and the expression of M1-type markers in microglia. Interestingly, TSLP treatment also influenced the differentiation of microglia towards the M2 type, suppressing LPS-induced activation, mediated by the JAK2/STAT5 pathway. Moreover, TSLP also promoted the expression of macrophage markers in the absence of LPS. These findings support the hypothesis that TSLP plays a role in reducing neuroinflammation by blocking the JAK2/STAT5 pathway induced by LPS, thus indicating a regulatory role in the central nervous system. Targeting this cytokine might provide a novel strategy for controlling an inflammatory response in the central nervous system.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"34 3","pages":"21-27"},"PeriodicalIF":2.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Th1/Th2 cytokine profile in patients with acute and chronic calculus cholecystitis.","authors":"Liling Chen, Xinyuan Chen","doi":"10.1684/ecn.2023.0488","DOIUrl":"10.1684/ecn.2023.0488","url":null,"abstract":"<p><p>Relatively little is known about the relationship between Th1/Th2 cytokines and calculus cholecystitis (CC). The purpose of this study was to investigate the correlation between serum Th1 and Th2 cytokine expression and CC, including both acute and chronic cases. In total, 102 patients with chronic calculous cholecystitis (CCC), 64 patients with acute calculous cholecystitis (ACC), and 55 healthy controls (HCs) were recruited for the study. Serum concentration of Th1 (IL-2, TNF-α, IFN-γ) and Th2 cytokines (IL-4, IL-6, IL-10) was measured at admission and on the fifth day after cholecystectomy using flow cytometry. In addition, the ratio of IL-6/IL-10 was calculated. Correlation of the corresponding factors was then analysed, and univariate and multivariate Cox regression analyses were performed to identify independent markers of ACC severity. Compared to HCs, CCC patients exhibited significantly elevated expression levels of IL-6 and IL-10, while ACC patients demonstrated higher expression of IL-2, TNF-α, and IL-6/ IL-10 in addition to IL-6, and IL-10. In ACC patients, there was a strong positive correlation between IL-6 and IL-10 concentration, the expression of IL-2 was observed to positively correlate with serum ALT and AST concentration, and TNF-α expression positively correlated with the duration of hospitalization. Moreover, patients with moderate-to-severe ACC presented with higher expression of IL-10 compared to those with mild ACC. Cox regression analysis confirmed that IL-10 and IL-6 were independent factors for the severity of ACC. Following surgery, the levels of IL-6 and IL-6/IL-10 significantly decreased but did not fully return to baseline levels in ACC patients. Our study reveals atypical Th1/Th2 cytokine expression profiles in patients with acute and chronic CC, and further highlights the significant potential of these cytokines, particularly IL-6 and IL-10, in assessing the severity and progression of CC.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"34 3","pages":"22-28"},"PeriodicalIF":2.8,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibodies as tools in cytokine discovery and usage for diagnosis and therapy of inflammatory diseases.","authors":"Jo Van Damme,&nbsp;Ghislain Opdenakker,&nbsp;Sam Van Damme,&nbsp;Sofie Struyf","doi":"10.1684/ecn.2023.0484","DOIUrl":"https://doi.org/10.1684/ecn.2023.0484","url":null,"abstract":"<p><p>Polyclonal antisera from patients have been at the basis of the description of autoimmune diseases and today monoclonal antibodies are widely used in the therapy of cancer and many inflammatory diseases. How antisera and antibodies in combination with traditional in vitro and in vivo biological test systems have been instrumental reagents for the discovery of new cytokines is illustrated here for interleukin-1, -6 and -8. Furthermore, widely used immunological detection/quantification systems, such as ELISAs and multiplex assays, based on the use of either polyclonal or monoclonal antibodies, are often fraught with misinterpretations, because the results are affected by the possible occurrence of posttranslational modifications (PTMs) of the analytes. Cytokines and chemokines are present in vivo as mixtures of proteoforms with different amino- or carboxytermini or carrying heterogeneous glycan chains and possibly also being subject to citrullination, pyroglutamination and other PTMs. Increased knowledge about the specificities of antibody (cross)reactivities with cytokine ligands have improved diagnosis and treatment of many diseases, with inflammatory processes, including cancer-associated inflammation, at the frontline.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"34 1","pages":"1-9"},"PeriodicalIF":2.8,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10114469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetylcholine suppresses LPS-induced endothelial cell activation by inhibiting the MAPK and NF-κB pathways.","authors":"Ping Li,&nbsp;Kewen Zhou,&nbsp;Jiehao Li,&nbsp;Xiaodan Xu,&nbsp;Ling Wang,&nbsp;Tinghuai Wang","doi":"10.1684/ecn.2023.0481","DOIUrl":"https://doi.org/10.1684/ecn.2023.0481","url":null,"abstract":"<p><strong>Background and objective: </strong>Endothelial cell activation plays a critical role in leukocyte recruitment during inflammation and infection. We previously found that cholinergic stimulation (via vagus nerve stimulation) attenuates vascular endothelial impairment and reduces the inflammatory profile in ovariectomized rats. However, the specific molecular mechanism is unclear. This study was designed to explore the effects and molecular mechanisms of cholinergic agonists (acetylcholine [ACh]) on lipopolysaccharide (LPS)-induced endothelial cell activation in vitro.</p><p><strong>Methods: </strong>Human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of LPS (10/100/1000 ng/mL) to activate endothelial cells. HUVECs were untreated, treated with ACh (10-5 M) alone, treated with 100 ng/mL LPS alone, or treated with different concentrations of ACh (10-9/10-8/10-7/10-6/10-5 M) before LPS stimulation. HUVECs were also pre-treated with 10-6 M ACh with or without mecamylamine (an nAChR blocker) (10 μΜ) and methyllycaconitine (a specific α7 nAChR blocker) (10 μΜ) and incubated with or without LPS. ELISA, western blotting, cell immunofluorescence, and cell adhesion assays were used to examine inflammatory cytokine production, adhesion molecule expression, monocyte-endothelial cell adhesion and activation of the MAPK/NF-κB pathways.</p><p><strong>Results: </strong>LPS (at 10 ng/mL, 100 ng/mL and 1,000 ng/mL) increased VCAM-1 expression in HUVECs in a dose-dependent manner (with no significant difference between LPS at 100 ng/mL and 1,000 ng/mL). ACh (10-9 M-10-5 M) blocked adhesion molecule expression (VCAM-1, ICAM-1, and E-selectin) and inflammatory cytokine production (TNF-α, IL-6, MCP-1, IL-8) in response to LPS in a dose-dependent manner (with no significant difference between 10-5 and 10-6 M Ach). LPS was also shown to significantly enhance monocyte-endothelial cell adhesion, which was largely abrogated by treatment with ACh (10-6M). VCAM-1 expression was blocked by mecamylamine rather than methyllycaconitine. Lastly, ACh (10-6 M) significantly reduced LPS-induced phosphorylation of NF-κB/p65, IκBα, ERK, JNK and p38 MAPK in HUVECs, which was blocked by mecamylamine.</p><p><strong>Conclusions: </strong>ACh protects against LPS-induced endothelial cell activation by inhibiting the MAPK and NF-κB pathways, which are mediated by nAChR, rather than α7 nAChR. Our results may provide novel insight into the anti-inflammatory effects and mechanisms of ACh.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"33 4","pages":"79-89"},"PeriodicalIF":2.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9962808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of immunomodulatory effects of co-culture or supernatant of dexamethasone or IFN-γ-treated adipose-derived mesenchymal stem cells on spleen mononuclear cells","authors":"Fatemeh Bayati,&nbsp;Maryam Valadi,&nbsp;Armin Ahmadi,&nbsp;Farangis Najafi,&nbsp;Bita Ansaripour,&nbsp;Ehsan Sharif-Paghaleh","doi":"10.1684/ecn.2022.0482","DOIUrl":"https://doi.org/10.1684/ecn.2022.0482","url":null,"abstract":"<p><p>Although mesenchymal stem cells (MSCs) have exhibited promising immunomodulatory potential in preclinical studies, clinical studies have revealed variable results. These results often depend on environmental cues. Pre-conditioning MSCs with cytokines is one of the methods used to enhance their immunomodulatory effects. In this study, we harvested adipose-derived MSCs from mice and cultured them with different doses of the cytokine, IFN-γ, and the corticosteroid drug, dexamethasone, in order to investigate their effects on MSC immunosuppressive function. We found the co-culture or supernatant of MSCs, pre-conditioned with IFN-γ, together with spleen mononuclear cells resulted in a significant reduction of mononuclear cell proliferation. Although the supernatant of MSCs, pre-conditioned with dexamethasone, showed similar results, dexamethasone pre-conditioning of co-cultured MSCs increased mononuclear cell proliferation. The results further our understanding of immune-related effects of MSCs which may provide a basis for further in vivo studies to achieve better clinical results. We propose that pre-conditioning with cytokines might be an effective method to boost the immunomodulatory effects of MSCs.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"33 3","pages":"70-78"},"PeriodicalIF":2.8,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10134695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9360292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical relevance and therapeutic potential of IL-38 in immune and non-immune-related disorders","authors":"Mohammad Reza Haghshenas,&nbsp;Mina Roshan Zamir,&nbsp;Mahboubeh Sadeghi,&nbsp;Mohammad Javad Fattahi,&nbsp;Kimia Mirshekari,&nbsp;Abbas Ghaderi","doi":"10.1684/ecn.2022.0480","DOIUrl":"https://doi.org/10.1684/ecn.2022.0480","url":null,"abstract":"<p><p>Interleukin-38 (IL-38) is the most recent member of the IL-1 family that acts as a natural inflammatory inhibitor by binding to cognate receptors, particularly the IL-36 receptor. In vitro, animal and human studies on autoimmune, metabolic, cardiovascular and allergic diseases, as well sepsis and respiratory viral infections, have shown that IL-38 exerts an anti-inflammatory activity by modulating the generation and function of inflammatory cytokines (e.g. IL-6, IL-8, IL-17 and IL-36) and regulating dendritic cells, M2 macrophages and regulatory T cells (Tregs). Accordingly, IL-38 may possess therapeutic potential for these types of diseases. IL-38 down-regulates CCR3+ eosinophil cells, CRTH2+ Th2 cells, Th17 cells, and innate lymphoid type 2 cells (ILC2), but up-regulates Tregs, and this has influenced the design of immunotherapeutic strategies based on regulatory cells/cytokines for allergic asthma in future studies. In auto-inflammatory diseases, IL-38 alleviates skin inflammation by regulating γδ T cells and limiting the production of IL-17. Due to its ability to suppress IL-1β, IL-6 and IL-36, this cytokine could reduce COVID-19 severity, and might be employed as a therapeutic tool. IL-38 may also influence host immunity and/or the components of the cancer microenvironment, and has been shown to improve the outcome of colorectal cancer, and may participate in tumour progression in lung cancer possibly by modulating CD8 tumour infiltrating T cells and PD-L1 expression. In this review, we first briefly present the biological and immunological functions of IL-38, and then discuss the important roles of IL-38 in various types of diseases, and finally highlight its use in therapeutic strategies.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"33 3","pages":"54-69"},"PeriodicalIF":2.8,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10134710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9360293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Interleukin-33 with Recurrent Pregnancy Loss in Egyptian Women","authors":"Lamyaa Salem,&nbsp;Ebtihal Eltaieb,&nbsp;Mariam Fathy Abdelmaksoud","doi":"10.1684/ecn.2022.0478","DOIUrl":"https://doi.org/10.1684/ecn.2022.0478","url":null,"abstract":"<p><strong>Background: </strong>A successful pregnancy requires a distinct and complex immunological state. Cytokines appear to be critical for the establishment of a tolerogenic environment towards the semi-allogenic foetus during the foeto-maternal interphase, and a shift from a Th1- to a Th2-cytokine profile may be crucial. An imbalance of cytokines can be a significant factor in recurrent pregnancy loss (RPL). Interleukin-33 (IL-33) is a member of the IL- 1 cytokine family, involved in both the innate and adaptive immune responses coordinating immune cell function for a broad range of physiological and pathological processes, including the regulation of pregnancy outcome.</p><p><strong>Objectives: </strong>The aim of this study was to investigate a possible association between IL-33 and RPL in Egyptian women.</p><p><strong>Methods: </strong>The study was conducted on 66 Egyptian females recruited from Ain Shams University Specialized Hospital and 66 matched healthy non-pregnant females of typical childbearing age without a history of RPL. Serum IL-33 was measured in all subjects using a sandwich ELISA technique.</p><p><strong>Results: </strong>Serum IL-33 levels were significantly higher in patients with RPL than in the healthy control group. In addition, in the patient group, there was a positive correlation between serum IL-33 level and both age and number of miscarriages and a negative correlation between serum IL-33 level and the number of deliveries.</p><p><strong>Conclusion: </strong>In Egyptian women, serum levels of IL-33 are associated with RPL, thus IL-33 level could be a predictive biomarker for RPL in early pregnancy.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"33 2","pages":"23-42"},"PeriodicalIF":2.8,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9117724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toll-like receptor agonists, poly(I:C) and flagellin, lead to IL-36γ induction with divergent release kinetics and differentially alter autophagy in primary human keratinocytes","authors":"Christopher J Papayannakos,&nbsp;Daniel Zhu,&nbsp;Bongseok Jung,&nbsp;Ali A Rana,&nbsp;James A DeVoti,&nbsp;Allan L Abramson,&nbsp;Vincent R Bonagura,&nbsp;Bettie M Steinberg","doi":"10.1684/ecn.2022.0479","DOIUrl":"https://doi.org/10.1684/ecn.2022.0479","url":null,"abstract":"<p><p>IL-36γ, a pro-inflammatory member of the IL-1 cytokine superfamily, can be induced and secreted by normal human foreskin keratinocytes (HFKs) in response to pathogenic stimuli, however, the mechanisms underlying the secretion are unknown. In this study, we demonstrate that stimulation with the TLR3 agonist, poly (I:C), led to a delayed secretion of IL-36γ compared to stimulation with the TLR5 agonist, flagellin, despite equal levels of the cytokine (p = 0.006). IL-36γ was shown to be released from HFKs in its inactive, uncleaved form, based on western blotting. Moreover, recombinant IL-36γ in its activated, cleaved form induced endogenous IL-36γ 10-fold (p = 0.004) and CXCL8 five-fold (p = 0.003) over baseline levels compared to unactivated full-length recombinant IL-36γ. The ratio of LC3b-II/LC3b-I was significantly higher in poly(I:C)-treated cells compared to flagellin-treated and unstimulated controls without a change in SQSTM1/p62 after 24 hours of stimulation (p = 0.043). Under fluorescence microscopy, poly(I:C) led to a two-fold increase at eight hours and four-fold increase at 24 hours in accumulated autophagosomes post-stimulation (p = 0.032). In contrast, autophagosomes were unchanged relative to baseline in response to flagellin. Bafilomycin A1 treatment enhanced poly(I:C)-mediated IL-36γ secretion (p = 0.044) while rapamycin led to a noticeable, but non-significant, increase in flagellin-mediated IL-36γ secretion, indicating that interrupting autophagic flux can alter IL-3γ grelease from HFKs. Finally, we show that, compared to clinically normal laryngeal tissue, there were significantly higher levels of LC3b-II in HPV-infected respiratory papilloma tissue, indicating a higher number of autophagosomes; a signature of disrupted autophagic flux.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"33 2","pages":"43-53"},"PeriodicalIF":2.8,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9117728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Th1 cytokine endotype discriminates and predicts severe complications in COVID-19","authors":"Takehiro Hasegawa,&nbsp;Takashi Hato,&nbsp;Toshitsugu Okayama,&nbsp;Kazuho Ikeo,&nbsp;Yoshiaki Miyamoto,&nbsp;Niina Iwanaga,&nbsp;Kohjin Suzuki,&nbsp;Maho Yoshida,&nbsp;Kazuto Yamashita,&nbsp;Saya Yamashita,&nbsp;Eiya Tamada,&nbsp;Abdullah Khasawneh,&nbsp;Faith Jessica Paran,&nbsp;Rieko Oyama,&nbsp;Toshio Naito,&nbsp;Kenta Noda,&nbsp;Yoko Tabe","doi":"10.1684/ecn.2022.0477","DOIUrl":"https://doi.org/10.1684/ecn.2022.0477","url":null,"abstract":"<p><p>Treatment of severe and critical cases of coronavirus disease 2019 (COVID-19) is still a top priority in public health. Previously, we reported distinct Th1 cytokines related to the pathophysiology of severe COVID-19 condition. In the present study, we investigated the association of Th1 and Th2 cytokine/chemokine endotypes with cell-mediated immunity via multiplex immunophenotyping, single-cell RNA-Seq analysis of peripheral blood mononuclear cells, and analysis of the clinical features of COVID-19 patients. Based on serum cytokine and systemic inflammatory markers, COVID-19 cases were classified into four clusters of increasing (I-IV) severity. Two prominent clusters were of interest and could be used as prognostic reference for a targeted treatment of severe COVID-19 cases. Cluster III reflected severe/critical pathology and was characterized by decreased in CCL17 levels and increase in IL-6, C-reactive protein CXCL9, IL-18, and IL-10 levels. The second cluster (Cluster II) showed mild to moderate pathology and was characterized by predominated CXCL9 and IL-18 levels, levels of IL-6 and CRP were relatively low. Cluster II patients received anti-inflammatory treatment in early-stage, which may have led prevent disease prognosis which is accompanied to IL-6 and CRP induction. In Cluster III, a decrease in the proportion of effector T cells with signs of T cell exhaustion was observed. This study highlights the mechanisms of endotype clustering based on specific inflammatory markers in related the clinical outcome of COVID-19.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"33 2","pages":"25-36"},"PeriodicalIF":2.8,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9595088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9117725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of effective factors on IL-10 signaling in B cells in patients with selective IgA deficiency","authors":"Yasser Bagheri,&nbsp;Mohsen Saeidi,&nbsp;Reza Yazdani,&nbsp;Fateme Babaha,&nbsp;Reza Falak,&nbsp;Gholamreza Azizi,&nbsp;Marjan Taherian,&nbsp;Fereshteh Salami,&nbsp;Yaghoob Yazdani,&nbsp;Somayeh Sadani,&nbsp;Ali Hosseini,&nbsp;Morteza Motallebnezhad,&nbsp;Hassan Abolhassani,&nbsp;Mehdi Shekarabi,&nbsp;Asghar Aghamohammadi","doi":"10.1684/ecn.2021.0464","DOIUrl":"https://doi.org/10.1684/ecn.2021.0464","url":null,"abstract":"<p><strong>Background: </strong>Selective IgA deficiency is the most prevalent form of primary immunodeficiencies. The pathogenesis of the disease is still unknown. Several studies have suggested a defect in B cell responses to IL-10; however, the main reason for this defect has not been reported. Elucidating IL-10 signaling defects and their correlation with clinical manifestations could be helpful for better understanding and treatment of the disease.</p><p><strong>Methods: </strong>In this study, 15 SIgAD patients and 15 age- and sex-matched healthy controls were included. Surface expression of transforming growth factor β receptor II (TGF-β RII), IL-10R and IgA was assessed by flow cytometry in human purified B cells before and after stimulation by IL-10. Protein expression of STAT3, p-STAT3 and SOCS3 was measured by Western blotting analysis. TGF-β and IgA secretion was evaluated by ELISA. Finally, the measurement of B cell apoptosis was performed by flow cytometry.</p><p><strong>Results: </strong>The TGF-βRII expression level was decreased after stimulation with IL-10 in patients compared with controls. Notably, the TGF-β level were higher after stimulation with mCD40L and IL-10 in the control group as compared to stimulation with mCD40L alone. The IgA+ B cell percentage and IgA secretion levels were significantly increased in controls as compared with SIgAD patients. The relative concentration of the total STAT3 was decreased as compared with controls.</p><p><strong>Conclusion: </strong>The defect in IgA production in SIgAD patients could be due to inadequate B cell responses to IL-10 stimulation that probably originate from defective regulation of IL-10-mediated TGF-b ’symbol’ production TGF-β response by IL-10. Furthermore, it is suggested that the absence of STAT3 protein baseline expression could impair cytokine-mediated signaling such as thatinduced by IL-!0 and IL-21.</p>","PeriodicalId":11749,"journal":{"name":"European cytokine network","volume":"33 1","pages":"1-12"},"PeriodicalIF":2.8,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40354499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}