Immunology letters最新文献

{"title":"In adult X-CGD patients, regulatory T cells are expanded while activated T cells display a NOX2-independent ROS increase","authors":"Ilenia Cammarata ,&nbsp;Valeria Pinna ,&nbsp;Ilenia Pacella ,&nbsp;Ivano Rotella ,&nbsp;Annarosa Soresina ,&nbsp;Raffaele Badolato ,&nbsp;Alessandro Plebani ,&nbsp;Claudio Pignata ,&nbsp;Emilia Cirillo ,&nbsp;Anna Maria Zicari ,&nbsp;Francesco Violi ,&nbsp;Roberto Carnevale ,&nbsp;Lorenzo Loffredo ,&nbsp;Silvia Piconese","doi":"10.1016/j.imlet.2024.106839","DOIUrl":"10.1016/j.imlet.2024.106839","url":null,"abstract":"<div><p>The X-linked chronic granulomatous disease (X-CGD), a rare genetic disease characterised by recurrent infections, is caused by mutations of NOX2. Significant proportions of X-CGD patients display signs of immune dysregulation. Regulatory T cells (Tregs) are CD4⁺ <em>T</em> lymphocytes that expand in active inflammation and prevent autoimmune disorders. Here we asked whether X-CGD is associated to Treg dysfunctions in adult patients. To this aim, the frequency of Tregs was analysed through intracellular flow cytometry in a cohort of adult X-CGD patients, carriers and controls. We found that Tregs were significantly expanded and activated in blood of adult X-CGD patients, and this was associated with activation of conventional CD4⁺ <em>T</em> cells (Tconvs). T cell activation was characterised by accumulation of intracellular ROS, not derived from NOX2 but likely produced by cellular metabolism. The higher TNF production by Tconvs in X-CGD patients might contribute to the expansion of Tregs through the TNFR2 receptor. In summary, our data indicate that Tregs expand in adult X-CGD in response to immune activation, and that the increase of NOX2-independent ROS content is a feature of activated T cells.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247824000117/pdfft?md5=018d2bd30aff3660594e2c81b4f13871&pid=1-s2.0-S0165247824000117-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139658977","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":"IL-38 in Behçet's disease: Gene expression in bronchoalveolar lavage from patients having pulmonary involvement","authors":"Kamel Hamzaoui ,&nbsp;Sabrine Louhaichi ,&nbsp;Mariem Salhi ,&nbsp;Fayçal Haj Sassi ,&nbsp;Ahmed Laathar ,&nbsp;Agnes Hamzaoui","doi":"10.1016/j.imlet.2024.106840","DOIUrl":"10.1016/j.imlet.2024.106840","url":null,"abstract":"<div><p>The etiological complexity of Behçet disease (BD), an immune-mediated rare form of vasculitis characterized by multi-organ involvement, is still elusive due to an incomplete understanding of the synergy between genetic susceptibility, environmental triggers, and an abnormal immune response. The diagnosis of BD relies on clinical symptoms. Lung inflammatory disorders are severe conditions of patients with BD, here we focus on the expression of biomarkers in BD patients with pulmonary manifestations.</p><p>Aiming to identify additional discriminating biomarker patterns, we measured and compared protein and gene expression of IL-38 and a broad panel of selected genes in bronchoalveolar cells of patients suffering from BD with and without pulmonary involvement compared to controls. ELISA and RT-PCR analysis were applied.</p><p>The first principal analysis highlighted decreased IL-38 level in BD patients compared to Rheumatoid Arthritis (RA) patients and controls: BD patients expressed lower IL-38 levels, particularly in cases with pulmonary involvement. The area under the curve (AUC) of the receiver-operating characteristic curve showed that IL-38 may be an eventual biomarker for BD. Co-cultured recombinant IL-38 and stimulated memory PBMCs of active BD, were able to suppress IL-17 and NLRP3 inflammasome and ameliorate the secretion of IL-10 and TGFβ. Transcription factors of the IL-1 family (IL-1β, IL-18, IL-32, IL-33 and IL-37) along with IFN-γ, IL-17, RORγt, Foxp3, TGFβ, IL-10 and NLRP3 inflammasome were the parameters that are the main contributor to the segregation between BD with and without lung involvement.</p><p>Our results indicate that IL-38 might be involved in the pathogenesis of BD and the combined gene expression in BAL suggests distinct mechanisms governing the inflammatory disorders in the lung.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139658984","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":"Alterations of B-Cell subsets in Peripheral Blood from Adult Patients with Idiopathic Membranous Nephropathy","authors":"Huijing Wang ,&nbsp;Lan Lan ,&nbsp;Jiahui Wang ,&nbsp;Jianghua Chen ,&nbsp;Liang Xiao ,&nbsp;Fei Han","doi":"10.1016/j.imlet.2024.106838","DOIUrl":"10.1016/j.imlet.2024.106838","url":null,"abstract":"<div><h3>Objectives</h3><p>Idiopathic membranous nephropathy (MN) is an autoimmune disease characterized by specific antibodies. However, the underlying mechanisms by which lymphocytes promote the development of MN remain poorly understood. This study aims to determine the changes of B-cell subsets and their clinical significance in MN patients.</p></div><div><h3>Methods</h3><p>We included a cohort of 21 idiopathic MN patients with new onset or a relapse, 19 healthy controls (HCs) and 10 patients with minimal change disease (MCD). Immunohistochemistry and flow cytometry were performed to assess the B-cell infiltration in renal biopsy tissues and peripheral blood, respectively.</p></div><div><h3>Results</h3><p>Idiopathic MN patients (including new-onset and relapse groups) had lower percentages of marginal-zone B (MZB) and non-switched memory B cells, and higher percentages of plasmablasts than HCs (<em>P</em> &lt; 0.01). Particularly, the new-onset group had lower percentages of switched memory B cells and MZB cells, and higher percentages of Naïve B cells than HCs (<em>P</em>&lt;0.05). Interestingly, the percentage of plasmablasts was significantly correlated with urine protein to creatinine ratio, serum albumin, IgG, anti-M-type phospholipase A2 receptor antibody level and age in MN patients (<em>P</em> &lt; 0.05). MN with Ehrenreich-Churg stage Ⅱ-Ⅳ had a lower median percentage of MZB and non-switched memory B cells, while a higher median percentage of plasmablasts than those in MN patients with stage Ehrenreich-Churg I (<em>P</em> &lt; 0.05).</p></div><div><h3>Conclusion</h3><p>Idiopathic MN patients had specific changes in B-cell subsets proportions in peripheral blood. Further studies are needed to precisely determine the roles of B-cell subsets in MN.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139558042","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":"The evaluation of PD-1 and Tim-3 expression besides their related miRNAs in PBMCs of women with recurrent pregnancy loss","authors":"Hamid Ahmadi ,&nbsp;Mohammad Sadegh Soltani-Zangbar ,&nbsp;Mehdi Yousefi ,&nbsp;Behzad Baradaran ,&nbsp;Saro Bromand ,&nbsp;Leili Aghebati-Maleki ,&nbsp;Julia Szekeres-Bartho","doi":"10.1016/j.imlet.2024.106837","DOIUrl":"10.1016/j.imlet.2024.106837","url":null,"abstract":"<div><p>Recurrent pregnancy loss (RPL) is a multifactorial disorder, associated with immunologic abnormalities. During pregnancy, the maternal immune system uses different tolerance mechanisms to deal with a semi-allogenic fetus. The expression of immune checkpoints and their related miRNAs in immune cells can ensure pregnancy at the feto-maternal interface by modulating immune responses. This study aims to evaluate the expression of the immune checkpoint molecules PD-1 and Tim-3 on circulating T cells by flow cytometry, that of mir-138 and mir-155 in PBMCs by Real-time PCR, and the concentrations of TGF-β and IP-10 in the sera of women suffering from RPL as well as of gestational age-matched healthy pregnant women by ELISA. The percentage of PD-1 or Tim-3 expressing CD8⁺ T cells was significantly lower in RPL patients compared to the controls, while there was no significant difference in Tim-3 expression of CD4⁺ T cells between the two groups. The mRNA of both the PD-1 and Tim-3 genes were downregulated in PBMCs of RPL patients compared to controls, however, the difference was not statistically significant for Tim-3. The concentration of TGF-β was significantly lower and that of IP-10 was significantly higher in the sera of RPL patients than in those of the controls. The relative expression of mir-138 and miR-155 were significantly lower, in PBMCs of RPL patients than in those of healthy pregnant women. These data confirm that by affecting cytokine production, immune checkpoints, and microRNAs play a role in establishing the appropriate local immune environment for successful pregnancy. The wider analysis of immune checkpoints may also yield new biomarkers for the diagnosis and prevention of RPL.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139544643","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":"Could we use PD-1 and PD-L1 expression on lymphocytes and monocytes as predictive markers for prognosis of acute biliary pancreatitis?","authors":"Ufuk Oguz Idiz ,&nbsp;Basak Aru ,&nbsp;Cemal Kaya ,&nbsp;Kivanc Derya Peker ,&nbsp;Cihad Tatar ,&nbsp;Mert Guler ,&nbsp;Abdurrahman Tunay ,&nbsp;Gulderen Yanikkaya Demirel ,&nbsp;Ali Osman Gurol","doi":"10.1016/j.imlet.2024.106836","DOIUrl":"10.1016/j.imlet.2024.106836","url":null,"abstract":"<div><h3>Purpose</h3><p>This study aimed to assess the significance of immunophenotyping and serum cytokines in predicting the clinical progression of acute biliary pancreatitis (ABP).</p></div><div><h3>Materials and methods</h3><p>Cytokine levels, T-helper, cytotoxic T, natural killer (NK) cells, monocytes, HLA-DR, and PD-1, as well as PDL-1 immune checkpoints, were measured in ABP patients at the time of diagnosis and compared with results from healthy volunteers. The study also compared leukocyte counts, hematocrit, immunophenotyping results, cytokine statuses, and PD-1, PDL-1 expression between healthy volunteers and ABP subgroups categorized by pancreatitis severity.</p></div><div><h3>Results</h3><p>The study included 65 ABP patients and 20 healthy volunteers. Significant differences were observed between groups in hematocrit, leukocyte counts, total monocytes, lymphocytes, CD3⁺ total T cells, CD4⁺ Th cells, PD-1 expression on CD4⁺ and CD8⁺ <em>T</em> lymphocytes, HLA-DR expression on CD14⁺ monocytes, NK cells, PD-L1 expression on CD14+ monocytes, classical and intermediate monocytes, as well as levels of IL-6, IL-8, IL-10, IL-18, and IL-33 cytokines. Moderate correlations were found with lymphocyte counts, PD-1⁺CD4⁺ cells, PD-L1⁺CD14⁺ cells, and strong correlations with HLA-DR⁺CD14⁺ cells. Hematocrit, CD3⁺ total T cells, NK cells, CD4⁺PD-1 ⁺ <em>T</em> cells, and CD8⁺PD-1 ⁺ <em>T</em> cells showed independent associations with the severity of ABP. Lymphocyte counts, CD14⁺HLA-DR⁺ cells, CD14⁺PD-L1⁺ cells, CD4⁺PD-1 ⁺ <em>T</em> cells, classical, and intermediate monocytes exhibited the highest Area Under the Curve rates in determining organ failure.</p></div><div><h3>Conclusions</h3><p>Hematocrit, lymphocyte counts, CD14⁺HLA-DR⁺ cells, CD14⁺PD-L1⁺ cells, and intermediate monocytes emerged as parameters most closely associated with the severity and these parameters could be useful in predicting the severity of ABP.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139396808","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":"Expression of epidermal growth factor receptor (EGFR) in systemic sclerosis patients (SSc) and gastro-oesophageal reflux disease (GORD)","authors":"Andrea Pasta ,&nbsp;Francesco Calabrese ,&nbsp;Shirin Djahandideh Sheijani ,&nbsp;Manuele Furnari ,&nbsp;Edoardo G. Giannini ,&nbsp;Federica Grillo ,&nbsp;Elisa Marabotto ,&nbsp;Luca Mastracci ,&nbsp;Giuseppe Murdaca ,&nbsp;Simone Negrini ,&nbsp;Edoardo Vincenzo Savarino ,&nbsp;Vincenzo Savarino ,&nbsp;Patrizia Zentilin","doi":"10.1016/j.imlet.2023.106834","DOIUrl":"10.1016/j.imlet.2023.106834","url":null,"abstract":"<div><h3>Introduction</h3><p>Systemic sclerosis (SSc) affects the connective tissue and leads to an abnormal fibrotic process in the skin and internal organs. Epidermal Growth Factor Receptor (EGFR) is able to induce cell proliferation and differentiation, and its expression is increased in SSc patients with pulmonary artery hypertension and in skin biopsies in patients with scleroderma. To date, no data on esophageal expression of EGFR are available in SSc patients. We aimed to evaluate whether the pro-fibrogenic pathways of SSc may affect EGFR expression in the esophagus.</p></div><div><h3>Methods</h3><p>A retrospective analysis included patients with SSc and control subjects suffering from gastroesophageal reflux symptoms. Endoscopic assessment and histopathologic analyses were performed in all subjects and the presence of microscopic esophagitis was used to distinguish patients with normal esophageal mucosa and subjects with non-erosive reflux disease. EGFR expression was measured in all subjects.</p></div><div><h3>Results</h3><p>A total of 35 patients with SSc were included, while the control group included 67 non-SSc patients. EGFR expression at the Z-line was higher in SSc patients than non-SSc patients in absence of microscopic esophagitis (median 65 %, IQR 56–71 % vs 42 %, IQR 37–54 %, <em>p</em> &lt; 0.001). Microscopic esophagitis was found in 60 % of patients with SSc and 62.7 % of control patients, and EGFR expression was significantly higher in patients presenting microscopic esophagitis both in SSc and non-SSc patients.</p></div><div><h3>Conclusion</h3><p>The EGFR hyperexpression may be due to SSc and/or reflux-related damage in patients with microscopic esophagitis. Further studies are warranted to answer open questions and provide a possible role of EGFR in terms of diagnosis, prognosis, and therapy.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139067524","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":"Role of G-protein-coupled estrogen receptor in the pathogenesis of chronic asthma","authors":"Masamichi Itoga ,&nbsp;Yoshiko Ishioka ,&nbsp;Tomonori Makiguchi ,&nbsp;Hisashi Tanaka ,&nbsp;Kageaki Taima ,&nbsp;Norihiro Saito ,&nbsp;Hirofumi Tomita ,&nbsp;Sadatomo Tasaka","doi":"10.1016/j.imlet.2023.12.001","DOIUrl":"10.1016/j.imlet.2023.12.001","url":null,"abstract":"<div><h3>Background and Aim</h3><p>G protein-coupled estrogen receptor (GPER) is an estrogen receptor located on the plasma membrane. We previously reported that the administration of G-1, a GPER-specific agonist, suppressed development of acute ovalbumin (OVA)-induced asthma in a mouse model. Herein, we evaluate the involvement of GPER in a mouse model of chronic OVA asthma.</p></div><div><h3>Methods</h3><p>G-1 or saline was administered subcutaneously to BALB/c mice with chronic OVA asthma, and pathological and immunological evaluation was performed. In addition, Foxp3-expressing CD4-positive T-cells in the spleen and ILC2 in the lungs were measured using flow cytometry.</p></div><div><h3>Results</h3><p>We observed a significant decrease in the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) in the G-1 treated group. In the airways, inflammatory cell accumulation, Th2 cytokines (IL-4, IL-5, IL-13, and eotaxin) and epithelial cytokine TSLP were suppressed, while in the BALF, anti-inflammatory cytokines (IL-10 and TGF-β) were increased. Furthermore, in splenic mononuclear cells, Foxp3-expressing CD4-positive T-cells were increased in the G-1 group, whereas treatment with G-1 did not change the percentage of ILC2 in the lungs.</p></div><div><h3>Conclusion</h3><p>G-1 administration suppressed allergic airway inflammation in mice with chronic OVA asthma. GPER may be a potential therapeutic target for chronic allergic asthma.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S016524782300202X/pdfft?md5=37af4ab8d4c9214e31217587fe71ab13&pid=1-s2.0-S016524782300202X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139027878","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":"Adenine is an anti-inflammatory metabolite found to be more abundant in M-CSF over GM-CSF-differentiated human macrophages","authors":"Karl J Harber ,&nbsp;Thuc-Anh Nguyen ,&nbsp;Bauke V Schomakers ,&nbsp;Daan A F Heister ,&nbsp;Helga E. de Vries ,&nbsp;Michel van Weeghel ,&nbsp;Jan Van den Bossche ,&nbsp;Menno P J de Winther","doi":"10.1016/j.imlet.2023.12.003","DOIUrl":"10.1016/j.imlet.2023.12.003","url":null,"abstract":"<div><p>Immunometabolism has been unveiled in the last decade to play a major role in controlling macrophage metabolism and inflammation. There has been a constant effort to understand the immunomodulating properties of regulated metabolites during inflammation with the aim of controlling and re-wiring aberrant macrophages in inflammatory diseases. M-CSF and GM-CSF-differentiated macrophages play a key role in mounting successful innate immune responses. When a resolution phase is not achieved however, GM-CSF macrophages contribute substantially more towards an adverse inflammatory milieu than M-CSF macrophages, consequently driving disease progression. Whether there are specific immunometabolites that determine the homoeostatic or inflammatory nature of M-CSF and GM-CSF-differentiated macrophages is still unknown. As such, we performed metabolomics analysis on LPS and IL-4-stimulated M-CSF and GM-CSF-differentiated human macrophages to identify differentially accumulating metabolites. Adenine was distinguished as a metabolite significantly higher in M-CSF-differentiated macrophages after both LPS or IL-4 stimulation. Human macrophages treated with adenine before LPS stimulation showed a reduction in inflammatory gene expression, cytokine secretion and surface marker expression. Adenine caused macrophages to become more quiescent by lowering glycolysis and OXPHOS which resulted in reduced ATP production. Moreover, typical metabolite changes seen during LPS-induced macrophage metabolic reprogramming were absent in the presence of adenine. Phosphorylation of metabolic signalling proteins AMPK, p38 MAPK and AKT were not responsible for the suppressed metabolic activity of adenine-treated macrophages. Altogether, in this study we highlight the immunomodulating capacity of adenine in human macrophages and its function in driving cellular quiescence.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247823002043/pdfft?md5=3d1a287f3ae320eb86cf0c1786e30f9d&pid=1-s2.0-S0165247823002043-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139027592","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":"CD36 as a double-edged sword in cancer","authors":"Muwei Jiang,&nbsp;Renske Karsenberg,&nbsp;Frans Bianchi,&nbsp;Geert van den Bogaart","doi":"10.1016/j.imlet.2023.12.002","DOIUrl":"10.1016/j.imlet.2023.12.002","url":null,"abstract":"<div><p>The membrane protein CD36 is a lipid transporter, scavenger receptor, and receptor for the antiangiogenic protein thrombospondin 1 (TSP1). CD36 is expressed by cancer cells and by many associated cells including various cancer-infiltrating immune cell types. Thereby, CD36 plays critical roles in cancer, and it has been reported to affect cancer growth, metastasis, angiogenesis, and drug resistance. However, these roles are partly contradictory, as CD36 has been both reported to promote and inhibit cancer progression. Moreover, the mechanisms are also partly contradictory, because CD36 has been shown to exert opposite cellular effects such as cell division, senescence and cell death. This review provides an overview of the diverse effects of CD36 on tumor progression, aiming to shed light on its diverse pro- and anti-cancer roles, and the implications for therapeutic targeting.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247823002031/pdfft?md5=f69bbdddc612d63dfb8ff7469782a332&pid=1-s2.0-S0165247823002031-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138829620","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":"Mettl3/Ythdf2 regulate macrophage inflammation and ROS generation by controlling Pyk2 mRNA stability","authors":"Yongjie Cai ,&nbsp;Ruiqing Yu ,&nbsp;Zhanqi Zhang ,&nbsp;Di Li ,&nbsp;Baicheng Yi ,&nbsp;Zhihui Feng ,&nbsp;Qiong Xu","doi":"10.1016/j.imlet.2023.11.004","DOIUrl":"10.1016/j.imlet.2023.11.004","url":null,"abstract":"<div><p>As one of the most prevalent modifications on RNA, N6-methyladenosine (m⁶A) has been recently found implicated in various pathological processes. Emerging studies have demonstrated the role of m⁶A and its writer Mettl3 in fine-tuning the immune response, which now becomes a research hotspot owing to its potential therapeutic value. However, the results are inconsistent and even contradictory, suggesting that there might be multiple Mettl3 target genes involved in different pathways. To delve deeper into the function of Mettl3 in the cellular inflammatory response, we first conducted bioinformatics analysis using RNA-seq in Mettl3 ablation macrophages, and found that Mettl3 might attenuate LPS-induced proinflammatory pathways and reactive oxygen species (ROS) generation process. Mettl3 knockdown significantly increased the LPS-induced IL-6, TNF-α, NOXs (Nox1, Nox2, Ncf1, and Ncf2) expression, ROS generation, and the phosphorylation of MAPKs and AKT signaling. Combining the results of RNA-seq and m⁶A mapping, we found that Pyk2 might be the target gene of Mettl3 affecting the inflammatory response. Mettl3 and Ythdf2 depletion increased the expression and mRNA stability of Pyk2, and RIP-PCR showed that Ythdf2 directly targeting Pyk2 was Mettl3 dependent. Moreover, the upregulated expression of TNF-α, IL-6, NOXs, ROS generation, and the phosphorylation of MAPKs and AKT signaling were downregulated by Pyk2 inhibitor in Mettl3 knockdown cells. All of these results suggest that Mettl3 regulates the mRNA stability and expression of Pyk2 in a Ythdf2-dependent way, which consequently triggers the activation of MAPKs and AKT signaling and upregulation of NOXs, thus promoting the generation of proinflammatory cytokines and ROS.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89718140","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}