Immunologic Research最新文献

{"title":"The combination of IDO and AHR blockers reduces the migration and clonogenicity of breast cancer cells.","authors":"Maryam Soltani-Asl, Parviz Azimnasab-Sorkhabi, Tulio Teruo Yoshinaga, Cristina de Oliveira Massoco, Jose Roberto Kfoury","doi":"10.1007/s12026-023-09450-9","DOIUrl":"10.1007/s12026-023-09450-9","url":null,"abstract":"<p><p>The indoleamine-2,3-dioxygenase (IDO) enzyme causes immunosuppressive consequences in the tumor microenvironment (TME). In addition, the role of aryl hydrocarbon receptor (AHR) in the TME is under discussion. The current study evaluated the role of the IDO and AHR blockers on cell migration, clonogenic, and IDO expression of murine breast cancer cells. The cell migration and clonogenic abilities of breast cancer cells are evaluated by wound‑healing assay (cell migration assay) and Colony formation assay (clonogenic assay). Also, flow cytometry analysis was used to detect the IDO-positive breast cancer cells. The results showed that treating cells with a combination of IDO and AHR blockers dramatically reduced breast cancer cells' migration and clonogenic capacities. Treating cells with only AHR blockade suppressed the clonogenic rate. Since both IDO and AHR are involved in their complex molecular networks, blocking both IDO and AHR might cause alterations in their molecular networks resulting in diminishing the migration and clonogenic abilities of breast cancer cells. However, further investigations are required to confirm our findings within in vivo models as a novel therapy for breast cancer.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048677","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":"Characteristics of splenic PD-1⁺ γδT cells in Plasmodium yoelii nigeriensis infection.","authors":"Dianhui Chen, Feng Mo, Meiling Liu, Lin Liu, Junmin Xing, Wei Xiao, Yumei Gong, Shanni Tang, Zhengrong Tan, Guikuan Liang, Hongyan Xie, Jun Huang, Juan Shen, Xingfei Pan","doi":"10.1007/s12026-023-09441-w","DOIUrl":"10.1007/s12026-023-09441-w","url":null,"abstract":"<p><p>Although the functions of programmed death-1 (PD-1) on αβ T cells have been extensively reported, a role for PD-1 in regulating γδT cell function is only beginning to emerge. Here, we investigated the phenotypic and functional characteristics of PD-1-expressing γδT cells, and the molecular mechanism was also explored in the Plasmodium yoelii nigeriensis (P. yoelii NSM)-infected mice. Flow cytometry and single-cell RNA sequencing (scRNA-seq) were performed. An inverse agonist of RORα, SR3335, was used to investigate the role of RORα in regulating PD-1⁺ γδT cells. The results indicated that γδT cells continuously upregulated PD-1 expression during the infection period. Higher levels of CD94, IL-10, CX3CR1, and CD107a; and lower levels of CD25, CD69, and CD127 were found in PD-1⁺ γδT cells from infected mice than in PD-1^- γδT cells. Furthermore, GO enrichment analysis revealed that the marker genes in PD-1⁺ γδT cells were involved in autophagy and processes utilizing autophagic mechanisms. ScRNA-seq results showed that RORα was increased significantly in PD-1⁺ γδT cells. GSEA identified that RORα was mainly involved in the regulation of I-kappaB kinase/NF-κB signaling and the positive regulation of cytokine production. Consistent with this, PD-1-expressing γδT cells upregulated RORα following Plasmodium yoelii infection. Additionally, in vitro studies revealed that higher levels of p-p65 were found in PD-1⁺ γδT cells after treatment with a RORα selective synthetic inhibitor. Collectively, these data suggest that RORα-mediated attenuation of NF-κB signaling may be fundamental for PD-1-expressing γδT cells to modulate host immune responses in the spleen of Plasmodium yoelii nigeriensis-infected C57BL/6 mice, and it requires further investigation.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11217126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139541188","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":"Evolutionary preservation of CpG dinucleotides in RAG1 may elucidate the relatively high rate of methylation-mediated mutagenesis of RAG1 transposase.","authors":"Mariam M Fawzy, Maiiada H Nazmy, Azza A K El-Sheikh, Moustafa Fathy","doi":"10.1007/s12026-023-09451-8","DOIUrl":"10.1007/s12026-023-09451-8","url":null,"abstract":"<p><p>Recombination-activating gene 1 (RAG1) is a vital player in V(D)J recombination, a fundamental process in primary B cell and T cell receptor diversification of the adaptive immune system. Current vertebrate RAG evolved from RAG transposon; however, it has been modified to play a crucial role in the adaptive system instead of being irreversibly silenced by CpG methylation. By interrogating a range of publicly available datasets, the current study investigated whether RAG1 has retained a disproportionate level of its original CpG dinucleotides compared to other genes, thereby rendering it more exposed to methylation-mediated mutation. Here, we show that 57.57% of RAG1 pathogenic mutations and 51.6% of RAG1 disease-causing mutations were associated with CpG methylation, a percentage that was significantly higher than that of its RAG2 cofactor alongside the whole genome. The CpG scores and densities for all RAG ancestors suggested that RAG transposon was CpG denser. The percentage of the ancestral CpG of RAG1 and RAG2 were 6% and 4.2%, respectively, with no preference towards CG containing codons. Furthermore, CpG loci of RAG1 in sperms were significantly higher methylated than that of RAG2. In conclusion, RAG1 has been exposed to CpG mediated methylation mutagenesis more than RAG2 and the whole genome, presumably due to its late entry to the genome later with an initially higher CpG content.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11217092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139491106","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":"Rituximab alleviates pediatric systemic lupus erythematosus associated refractory immune thrombocytopenia: a case-based review.","authors":"Fangxin Mu, Xue Bai, Yan Lou, Ping Luo, Qiaoyan Guo","doi":"10.1007/s12026-024-09454-z","DOIUrl":"10.1007/s12026-024-09454-z","url":null,"abstract":"<p><p>A complication of pediatric systemic lupus erythematosus (pSLE) is immune thrombocytopenia (ITP). Although corticosteroids and immunoglobulins are frequently used as preliminary treatments, some patients do not respond to them. Rituximab has been reported to be safe and effective in the treatment of pSLE complicated with refractory ITP. Research is currently underway to determine the optimal rituximab dose for these individuals. We report a case of a child with SLE-associated ITP (SLE-ITP) who was successfully treated with rituximab. Rituximab is likely the most viable therapeutic option for refractory SLE-ITP. Furthermore, a comprehensive review of the relevant literature was performed and a concise overview of the pathogenesis and available treatment modalities for pediatric patients diagnosed with SLE and concurrent ITP was provided.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139566163","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":"Correction to: Characteristics of splenic PD-1⁺ γδT cells in Plasmodium yoelii nigeriensis infection.","authors":"Dianhui Chen, Feng Mo, Meiling Liu, Lin Liu, Junmin Xing, Wei Xiao, Yumei Gong, Shanni Tang, Zhengrong Tan, Guikuan Liang, Hongyan Xie, Jun Huang, Juan Shen, Xingfei Pan","doi":"10.1007/s12026-024-09469-6","DOIUrl":"10.1007/s12026-024-09469-6","url":null,"abstract":"","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11217037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989980","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":"Response to: regarding the significance of anti-COVID-IgA antibody response in COVID-19 breakthrough infection.","authors":"Sabiha Anis, Mariam Ashfaq Khan, Areej Fatima, Fatima Kanani, Javeria Aijaz, Aneela Hussain, Samreen Sarfaraz","doi":"10.1007/s12026-023-09452-7","DOIUrl":"10.1007/s12026-023-09452-7","url":null,"abstract":"<p><p>In response to Chen et al.'s comments on our paper regarding the significance of anti-COVID-IgA antibody response in COVID-19 breakthrough infection in vaccinated patients, we have highlighted the role and the scope of this paper in this correspondence. The role of anti-COVID-19-IgA is already known. The objective of the previous study was to see its role in breakthrough-infected patients. To analyse this effect, we recruited patients with COVID-19 infection after they were fully vaccinated and compared them with the vaccinated group who did not get the infection. Both groups were equally exposed to the virus as all of them were health care workers. We also showed that the anti-COVID-19-NP-IgA was absent in the healthy cohort of our study groups, signifying the absence of natural infection in them during this period. The article also highlights the importance of vaccinating all individuals including those who are immunosuppressed, as it prevents severe COVID-19 infection in these individuals. The physicians should be aware of the fact that immunosuppressed patients are more likely to get COVID-19 breakthrough infection. However, proper vaccination with booster doses prevents severe infection in them.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139097757","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":"Serum soluble LYVE1 is a promising non-invasive biomarker of renal fibrosis: a population-based retrospective cross-sectional study.","authors":"Jing Liu, Yuqing Liu, Wenqian Zhou, Yiguo Liu, Saiya Zhu, Ying Yu, Jieli Huang, Chen Yu","doi":"10.1007/s12026-023-09448-3","DOIUrl":"10.1007/s12026-023-09448-3","url":null,"abstract":"<p><p>Diagnosis of renal fibrosis can only be verified by kidney biopsy, but biomarkers for non-invasive evaluation remain unsatisfactory. Patients with fibrosis often have abnormalities of the lymphatic vascular system and associated immune function. We describe here a lymphatic marker as a candidate biomarker for fibrosis. After assessing and grading the fibrosis scores, testing serum soluble lymphatic vessel endothelial hyaluronan receptor1 (sLYVE1) level, and collecting clinical information, the association between sLYVE1 and renal fibrosis was analyzed. Logistic regression analysis was used to screen variables. Diagnosis models with or without sLYVE1 were built, and nomograms were plotted. Calibration curve, C-index, and DCA were performed to assess the models. A total of 298 patients were enrolled in the study, of which 199 were included in the training cohort and 99 patients in the validation cohort. Serum sLYVE1 levels markedly elevated with increasing fibrosis grade (p<0.05). ROC analysis of sLYVE1 showed an AUC of 0.791 and 0.846 with optimal cut-off value of 405.25 ng/mL and 498.55 ng/mL for the prediction of moderate-to-severe renal fibrosis (MSF) and severe renal fibrosis (SF), respectively. The diagnostic nomogram model without sLYVE1 (model 1) included traditional clinical determinants (C-index: 0.658 for MSF; 0.603 for SF). A combination of model 1 and sLYVE1 (model 2) improved predictive performance (C-index: 0.847 for MSF; 0.856 for SF). Calibration curve and DCA demonstrated a better consistency accuracy and clinical benefit of model 2 than model 1. Serum sLYVE1 may be identified as a potential biomarker of renal fibrosis. Models incorporating sLYVE1 may be beneficial for a more accurate non-invasive diagnosis of renal fibrosis.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11217098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138884892","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":"The immunosuppressive landscape in tumor microenvironment","authors":"Wuyi Liu, Huyue Zhou, Wenjing Lai, Changpeng Hu, Rufu Xu, Peng Gu, Menglin Luo, Rong Zhang, Guobing Li","doi":"10.1007/s12026-024-09483-8","DOIUrl":"https://doi.org/10.1007/s12026-024-09483-8","url":null,"abstract":"<p>Recent advances in cancer immunotherapy, especially immune checkpoint inhibitors (ICIs), have revolutionized the clinical outcome of many cancer patients. Despite the fact that impressive progress has been made in recent decades, the response rate remains unsatisfactory, and many patients do not benefit from ICIs. Herein, we summarized advanced studies and the latest insights on immune inhibitory factors in the tumor microenvironment. Our in-depth discussion and updated landscape of tumor immunosuppressive microenvironment may provide new strategies for reversing tumor immune evasion, enhancing the efficacy of ICIs therapy, and ultimately achieving a better clinical outcome.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140834497","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":"SIT1 identifies circulating hypoactive T cells with elevated cytotoxic molecule secretion in systemic lupus erythematosus patients","authors":"Ainizati Hasimu, Ayibaota Bahabayi, Ziqi Xiong, Qi Li, Zhonghui Zhang, Xingyue Zeng, Mohan Zheng, Zihang Yuan, Chen Liu","doi":"10.1007/s12026-024-09481-w","DOIUrl":"https://doi.org/10.1007/s12026-024-09481-w","url":null,"abstract":"<p>This study aims to elucidate the expression and functionality of SIT1 in circulating CD8/CD4 + T cells in humans and to delineate its significance in systemic lupus erythematosus (SLE) patients. We employed multiparametric flow cytometry to investigate the expression of SIT1 in circulating CD8/CD4 + T cells and their respective subsets, comparing healthy controls (HCs) with SLE patients. Furthermore, we assessed the levels of granzyme B, perforin, IL-17, and IFN-γ in SIT1-related CD8/CD4 + T cells from both HCs and SLE patients, both before and after PMA stimulation. Clinically, we conducted receiver operating characteristic curve analysis and correlation analysis to evaluate the clinical relevance of SIT1-related CD8/CD4 + T cells in SLE patients. SIT1 exhibited higher expression in CD4 + T cells, with SIT1 − T cells demonstrating elevated levels of granzyme B, perforin, and IFN-γ compared to SIT1 + T cells. PMA-stimulated T cells exhibited reduced SIT1 expression compared to unstimulated T cells. SLE patients displayed increased SIT1 + proportions in CD8 + T cells and decreased SIT1 + CD4 + T cell numbers. Additionally, SIT1 + cells in SLE patients exhibited significantly higher levels of granzyme B and perforin compared to HCs. SIT1 + cells demonstrated significant associations with clinical indicators in SLE patients, with indicators related to SIT1 proving valuable in the diagnosis of SLE patients. SIT1 is inversely correlated with T cell activation. In SLE patients, SIT1 expression is altered in T cells concomitant with an augmented secretion of cytotoxic molecules. This upregulation may contribute to the pathogenesis of SLE and enhance its diagnostic potential.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>\u0000","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140834495","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":"FOXP4-AS1 promotes CD8+ T cell exhaustion and esophageal cancer immune escape through USP10-stabilized PD-L1","authors":"Guo-yi Shen, Yi Zhang, Rong-zhi Huang, Zhi-yong Huang, Le-yi Yang, Ding-zhu Chen, Shao-bin Yang","doi":"10.1007/s12026-024-09482-9","DOIUrl":"https://doi.org/10.1007/s12026-024-09482-9","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Esophageal cancer (EC) is the 9th most frequently diagnosed malignancy globally with unfavorable prognosis. Immune escape is one of the principal factors leading to poor survival, however, the mechanism underlying immune escape remains largely uninvestigated. The xenograft mouse model and EC cell-CD8⁺ cytotoxic T lymphocytes (CTLs) co-culture system were established. Immunohistochemistry, qRT-PCR or western blot were employed to detect the levels of long non-coding RNA (lncRNA) FOXP4-AS1, PD-L1, USP10 and other molecules. The abundance of T cells, cytokine production and cell apoptosis were monitored by flow cytometry. The viability of CTLs was assessed by Trypan blue staining. The binding between FOXP4-AS1 and USP10 was validated by RNA pull-down assay, and the interaction between USP10 and PD-L1, as well as the ubiquitination of PD-L1, were detected by co-immunoprecipitation. The elevation of FOXP4-AS1 in EC was associated with decreased CTL abundance, and upregulated PD-L1 facilitated CTL apoptosis in EC. FOXP4-AS1 accelerated EC tumor growth by decreasing the abundance of tumor infiltrating CTLs <i>in vivo</i>. FOXP4-AS1 inhibited the viability of CTLs and facilitated the cytotoxicity and exhaustion of CTLs. In Kyse 450 cell-CTL co-culture system, FOXP4-AS1 suppressed the viability and abundance of CTLs, and inhibited EC cell apoptosis via PD-L1. Mechanistically, FOXP4-AS1 regulated the ubiquitination of PD-L1 through deubiquitinating enzyme USP10. FOXP4-AS1 promoted CTL exhaustion and EC immune escape through USP10-stabilized PD-L1.</p><h3 data-test=\"abstract-sub-heading\">Highlights</h3><ul>\u0000<li>\u0000<p>PD-L1 facilitated CD8⁺ T cell apoptosis in EC.</p>\u0000</li>\u0000<li>\u0000<p>Upregulated FOXP4-AS1 promoted EC tumor growth by inhibiting the viability and facilitating the cytotoxicity and exhaustion of tumor infiltrating CD8⁺ T cells.</p>\u0000</li>\u0000<li>\u0000<p>FOXP4-AS1 suppressed the viability and abundance of CD8⁺ T cells through USP10-mediated deubiquitination of PD-L1.</p>\u0000</li>\u0000</ul>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140834508","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}