Hanae Miyazawa, Masahiro Muraoka, Yusuke Matsuda, T. Toma, Tomohiro Morio, T. Shigemura, Kohei Haraguchi, Tadashi Matsubayashi, T. Kawai, Yuya Shirai, T. Wada
{"title":"Clinical and molecular significance of flow cytometric analysis for reactive oxygen species production and residual p67phox expression in p67phox-deficient chronic granulomatous disease.","authors":"Hanae Miyazawa, Masahiro Muraoka, Yusuke Matsuda, T. Toma, Tomohiro Morio, T. Shigemura, Kohei Haraguchi, Tadashi Matsubayashi, T. Kawai, Yuya Shirai, T. Wada","doi":"10.1111/sji.13372","DOIUrl":"https://doi.org/10.1111/sji.13372","url":null,"abstract":"Chronic granulomatous disease (CGD) is a primary immunodeficiency disease caused by molecular defects in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. p67phox-CGD is an autosomal recessive CGD, which is caused by a defect in the cytosolic components of NADPH oxidase, p67phox, encoded by NCF2. We previously established a flow cytometric analysis for p67phox expression, which allows accurate assessment of residual protein expression in p67phox-CGD. We evaluated the correlation between oxidase function and p67phox expression, and assessed the relevancy to genotypes and clinical phenotypes in 11 patients with p67phox-CGD. Reactive oxygen species (ROS) production by granulocytes was evaluated using dihydrorhodamine-1,2,3 (DHR) assays. p67phox expression was evaluated in the monocyte population. DHR activity and p67phox expression were significantly correlated (r = 0.718, p < 0.0162). Additionally, DHR activity and p67phox expression were significantly higher in patients carrying one missense variant in combination with one nonsense or frameshift variant in the NCF2 gene than in patients with only null variants. The available clinical parameters of our patients (i.e., age at disease onset, number of infectious episodes, and each infection complication) were not linked with DHR activity or p67phox expression levels. In summary, our flow cytometric analysis revealed a significant correlation between residual ROS production and p67phox expression. More deleterious NCF2 genotypes were associated with lower levels of DHR activity and p67phox expression. DHR assays and protein expression analysis by using flow cytometry may be relevant strategies for predicting the genotypes of p67phox-CGD.","PeriodicalId":503453,"journal":{"name":"Scandinavian Journal of Immunology","volume":"15 12","pages":"e13372"},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140671299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaofang Xiong, Zheng Yan, Long Yan, Xuexue Yang, Dongsheng Li, Guizhen Lin
{"title":"Oxidized low‐density lipoproteins impair the pro‐atherosclerotic effect of granulocyte‐macrophage‐colony‐stimulating factor‐producing T helper cells on macrophages","authors":"Xiaofang Xiong, Zheng Yan, Long Yan, Xuexue Yang, Dongsheng Li, Guizhen Lin","doi":"10.1111/sji.13362","DOIUrl":"https://doi.org/10.1111/sji.13362","url":null,"abstract":"T cells contribute to the pathogenesis of atherosclerosis. However, the presence and function of granulocyte‐macrophage‐colony‐stimulating factor (GM‐CSF)‐producing T helper (ThGM) cells in atherosclerosis development is unknown. This study aims to characterize the phenotype and function of ThGM cells in experimental atherosclerosis. Atherosclerosis was induced by feeding apolipoprotein E knockout (ApoE−/−) mice with a high‐fat diet. Aortic ThGM cells were detected and sorted by flow cytometry. The effect of oxidized low‐density lipoprotein (oxLDL) on ThGM cells and the impact of ThGM cells on macrophages were evaluated by flow cytometry, quantitative RT‐PCR, oxLDL binding/uptake assay, immunoblotting and foam cell formation assay. We found that GM‐CSF+IFN‐γ− ThGM cells existed in atherosclerotic aortas. Live ThGM cells were enriched in aortic CD4+CCR6−CCR8−CXCR3−CCR10+ T cells. Aortic ThGM cells triggered the expression of interleukin‐1β (IL‐1β), tumour necrosis factor (TNF), interleukin‐6 (IL‐6) and C‐C motif chemokine ligand 2 (CCL2) in macrophages. Besides, aortic ThGM cells expressed higher CD69 than other T cells and bound to oxLDL. oxLDL suppressed the cytokine expression in ThGM cells probably via inhibiting the signal transducer and activator of transcription 5 (STAT5) signalling. Furthermore, oxLDL alleviated the effect of ThGM cells on inducing macrophages to produce pro‐inflammatory cytokines and generate foam cells. The nuclear receptor subfamily 4 group A (NR4A) members NR4A1 and NR4A2 were involved in the suppressive effect of oxLDL on ThGM cells. Collectively, oxLDL suppressed the supportive effect of ThGM cells on pro‐atherosclerotic macrophages.","PeriodicalId":503453,"journal":{"name":"Scandinavian Journal of Immunology","volume":"144 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139838165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Uzawa, M. Yasuda, Hiroyuki Akamine, Yosuke Onishi, Hideo Handa, Etsuko Ogaya, Y. Ozawa, H. Masuda, M. Mori, Satoshi Kuwabara
{"title":"Markedly upregulated serum semaphorin 4A as a novel activity marker of myasthenia gravis","authors":"A. Uzawa, M. Yasuda, Hiroyuki Akamine, Yosuke Onishi, Hideo Handa, Etsuko Ogaya, Y. Ozawa, H. Masuda, M. Mori, Satoshi Kuwabara","doi":"10.1111/sji.13360","DOIUrl":"https://doi.org/10.1111/sji.13360","url":null,"abstract":"Myasthenia gravis (MG) is an autoantibody‐mediated disease of the neuromuscular junction. Semaphorin 4A (Sema4A) is involved in the activation of T cells in various inflammatory disorders. In this study, we aimed to investigate whether Sema4A is involved in the pathogenesis of MG. We measured serum Sema4A concentrations in 30 treatment‐naïve MG patients with acetylcholine receptor (AChR) antibodies, 7 with muscle‐specific tyrosine kinase (MuSK) antibodies and 21 normal controls. As a result, serum Sema4A levels were significantly higher in patients with AChR antibody‐positive MG and MuSK antibody‐positive MG than in controls (p ≤ 0.0001 for both MG groups). Serum Sema4A levels were correlated with AChR antibody levels (Spearman's ρ = 0.39, p = 0.03) and MG Foundation of America clinical classification classes (Spearman's ρ = 0.38, p = 0.04) in patients with AChR antibody‐positive MG. In conclusion, high serum Sema4A levels may reflect T‐cell activation, and this molecule could be a potential marker of disease activity in MG.","PeriodicalId":503453,"journal":{"name":"Scandinavian Journal of Immunology","volume":"19 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139837247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Uzawa, M. Yasuda, Hiroyuki Akamine, Yosuke Onishi, Hideo Handa, Etsuko Ogaya, Y. Ozawa, H. Masuda, M. Mori, Satoshi Kuwabara
{"title":"Markedly upregulated serum semaphorin 4A as a novel activity marker of myasthenia gravis","authors":"A. Uzawa, M. Yasuda, Hiroyuki Akamine, Yosuke Onishi, Hideo Handa, Etsuko Ogaya, Y. Ozawa, H. Masuda, M. Mori, Satoshi Kuwabara","doi":"10.1111/sji.13360","DOIUrl":"https://doi.org/10.1111/sji.13360","url":null,"abstract":"Myasthenia gravis (MG) is an autoantibody‐mediated disease of the neuromuscular junction. Semaphorin 4A (Sema4A) is involved in the activation of T cells in various inflammatory disorders. In this study, we aimed to investigate whether Sema4A is involved in the pathogenesis of MG. We measured serum Sema4A concentrations in 30 treatment‐naïve MG patients with acetylcholine receptor (AChR) antibodies, 7 with muscle‐specific tyrosine kinase (MuSK) antibodies and 21 normal controls. As a result, serum Sema4A levels were significantly higher in patients with AChR antibody‐positive MG and MuSK antibody‐positive MG than in controls (p ≤ 0.0001 for both MG groups). Serum Sema4A levels were correlated with AChR antibody levels (Spearman's ρ = 0.39, p = 0.03) and MG Foundation of America clinical classification classes (Spearman's ρ = 0.38, p = 0.04) in patients with AChR antibody‐positive MG. In conclusion, high serum Sema4A levels may reflect T‐cell activation, and this molecule could be a potential marker of disease activity in MG.","PeriodicalId":503453,"journal":{"name":"Scandinavian Journal of Immunology","volume":"36 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139777541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaofang Xiong, Zheng Yan, Long Yan, Xuexue Yang, Dongsheng Li, Guizhen Lin
{"title":"Oxidized low‐density lipoproteins impair the pro‐atherosclerotic effect of granulocyte‐macrophage‐colony‐stimulating factor‐producing T helper cells on macrophages","authors":"Xiaofang Xiong, Zheng Yan, Long Yan, Xuexue Yang, Dongsheng Li, Guizhen Lin","doi":"10.1111/sji.13362","DOIUrl":"https://doi.org/10.1111/sji.13362","url":null,"abstract":"T cells contribute to the pathogenesis of atherosclerosis. However, the presence and function of granulocyte‐macrophage‐colony‐stimulating factor (GM‐CSF)‐producing T helper (ThGM) cells in atherosclerosis development is unknown. This study aims to characterize the phenotype and function of ThGM cells in experimental atherosclerosis. Atherosclerosis was induced by feeding apolipoprotein E knockout (ApoE−/−) mice with a high‐fat diet. Aortic ThGM cells were detected and sorted by flow cytometry. The effect of oxidized low‐density lipoprotein (oxLDL) on ThGM cells and the impact of ThGM cells on macrophages were evaluated by flow cytometry, quantitative RT‐PCR, oxLDL binding/uptake assay, immunoblotting and foam cell formation assay. We found that GM‐CSF+IFN‐γ− ThGM cells existed in atherosclerotic aortas. Live ThGM cells were enriched in aortic CD4+CCR6−CCR8−CXCR3−CCR10+ T cells. Aortic ThGM cells triggered the expression of interleukin‐1β (IL‐1β), tumour necrosis factor (TNF), interleukin‐6 (IL‐6) and C‐C motif chemokine ligand 2 (CCL2) in macrophages. Besides, aortic ThGM cells expressed higher CD69 than other T cells and bound to oxLDL. oxLDL suppressed the cytokine expression in ThGM cells probably via inhibiting the signal transducer and activator of transcription 5 (STAT5) signalling. Furthermore, oxLDL alleviated the effect of ThGM cells on inducing macrophages to produce pro‐inflammatory cytokines and generate foam cells. The nuclear receptor subfamily 4 group A (NR4A) members NR4A1 and NR4A2 were involved in the suppressive effect of oxLDL on ThGM cells. Collectively, oxLDL suppressed the supportive effect of ThGM cells on pro‐atherosclerotic macrophages.","PeriodicalId":503453,"journal":{"name":"Scandinavian Journal of Immunology","volume":"34 21","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139778445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to “Research progress on intestinal tissue‐resident memory T cells in inflammatory bowel disease”","authors":"","doi":"10.1111/sji.13355","DOIUrl":"https://doi.org/10.1111/sji.13355","url":null,"abstract":"","PeriodicalId":503453,"journal":{"name":"Scandinavian Journal of Immunology","volume":"29 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139386968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}