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Murine cytotoxic CD4+ T cells in the tumor microenvironment are at a hyper-maturation stage of Th1 CD4+ T cells sustained by IL-12. 肿瘤微环境中的小鼠细胞毒性CD4+ T细胞在IL-12的支持下处于Th1 CD4+ T细胞的超成熟阶段。
IF 4.4 4区 医学 Q2 Medicine Pub Date : 2023-08-07 DOI: 10.1093/intimm/dxad015
Yung-Chang Lin, Cheng-Heng Wu, Pin-Jung Chen, Chien-Hao Huang, Chan-Keng Yang, Avijit Dutta, Ching-Tai Huang, Chun-Yen Lin

The roles of tumor-infiltrating CD4+Foxp3- T cells are not well characterized due to their plasticity of differentiation, and varying levels of activation or exhaustion. To further clarify this issue, we used a model featuring subcutaneous murine colon cancer and analyzed the dynamic changes of phenotype and function of the tumor-associated CD4+ T-cell response. We found that, even at a late stage of tumor growth, the tumor-infiltrating CD4+Foxp3- T cells still expressed effector molecules, inflammatory cytokines and molecules that are expressed at reduced levels in exhausted cells. We used microarrays to examine the gene-expression profiles of different subsets of CD4+ T cells and revealed that the tumor-infiltrating CD4+Foxp3- T cells expressed not only type 1 helper (Th1) cytokines, but also cytolytic granules such as those encoded by Gzmb and Prf1. In contrast to CD4+ regulatory T cells, these cells exclusively co-expressed natural killer receptor markers and cytolytic molecules as shown by flow-cytometry studies. We used an ex vivo killing assay and proved that they could directly suppress CT26 tumor cells through granzyme B and perforin. Finally, we used pathway analysis and ex vivo stimulation to confirm that the CD4+Foxp3- T cells expressed higher levels of IL12rb1 genes and were activated by the IL-12/IL-27 pathway. In conclusion, this work finds that, in late-stage tumors, the tumor-infiltrating lymphocyte population of CD4+ cells harbored a sustained, hyper-maturated Th1 status with cytotoxic function supported by IL-12.

由于肿瘤浸润性CD4+Foxp3- T细胞的分化可塑性和不同程度的激活或衰竭,其作用尚未得到很好的表征。为了进一步澄清这一问题,我们采用小鼠皮下结肠癌模型,分析了肿瘤相关CD4+ t细胞反应的表型和功能的动态变化。我们发现,即使在肿瘤生长的后期,浸润肿瘤的CD4+Foxp3- T细胞仍然表达效应分子、炎症细胞因子和在衰竭细胞中表达水平降低的分子。我们利用微阵列技术检测了CD4+ T细胞不同亚群的基因表达谱,发现浸润肿瘤的CD4+Foxp3- T细胞不仅表达1型辅助细胞因子(Th1),还表达由Gzmb和Prf1编码的细胞溶解颗粒。流式细胞术研究显示,与CD4+调节性T细胞相比,这些细胞完全共表达自然杀伤受体标记物和细胞溶解分子。我们用离体杀伤实验证明它们可以通过颗粒酶B和穿孔素直接抑制CT26肿瘤细胞。最后,我们通过通路分析和离体刺激证实了CD4+Foxp3- T细胞表达更高水平的IL12rb1基因,并通过IL-12/IL-27途径被激活。总之,本研究发现,在晚期肿瘤中,浸润肿瘤的CD4+淋巴细胞群具有持续的、高度成熟的Th1状态,并具有IL-12支持的细胞毒性功能。
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引用次数: 0
Necessity of HuR/ELAVL1 for the activation-induced cytidine deaminase-dependent decrease in topoisomerase 1 in antibody diversification. HuR/ELAVL1在抗体多样化中激活诱导胞苷脱氨酶依赖性拓扑异构酶1减少的必要性。
IF 4.4 4区 医学 Q2 Medicine Pub Date : 2023-08-07 DOI: 10.1093/intimm/dxad011
Wajid Amin, Shoki Nishio, Tasuku Honjo, Maki Kobayashi

Activation-induced cytidine deaminase (AID)-dependent DNA cleavage is the initial event of antibody gene-diversification processes such as class switch recombination (CSR) and somatic hypermutation (SHM). We previously reported the requirement of an AID-dependent decrease of topoisomerase 1 (Top1) for efficient DNA cleavage, but the underlying molecular mechanism has remained elusive. This study focuses on HuR/ELAVL1, a protein that binds to AU-rich elements in RNA. HuR-knockout (KO) CH12 cells derived from murine B lymphoma cells were found to have lower CSR and hypermutation efficiencies due to decreased AID-dependent DNA cleavage levels. The HuR-KO CH12 cells do not show impairment in cell cycles and Myc expression, which have been reported in HuR-reduced spleen B cells. Furthermore, drugs that scavenge reactive oxygen species (ROS) do not rescue the lower CSR in HuR-KO CH12 cells, meaning that ROS or decreased c-Myc protein amount is not the reason for the deficiencies of CSR and hypermutation in HuR-KO CH12 cells. We show that HuR binds to Top1 mRNA and that complete deletion of HuR abolishes AID-dependent repression of Top1 protein synthesis in CH12 cells. Additionally, reduction of CSR to IgG3 in HuR-KO cells is rescued by knockdown of Top1, indicating that elimination of the AID-dependent Top1 decrease is the cause of the inefficiency of DNA cleavage, CSR and hypermutation in HuR-KO cells. These results show that HuR is required for initiation of antibody diversification and acquired immunity through the regulation of AID-dependent DNA cleavage by repressing Top1 protein synthesis.

激活诱导胞苷脱氨酶(AID)依赖的DNA切割是抗体基因多样化过程的初始事件,如类开关重组(CSR)和体细胞超突变(SHM)。我们之前报道了aids依赖性的拓扑异构酶1 (Top1)的减少对高效DNA切割的要求,但其潜在的分子机制仍然难以捉摸。这项研究的重点是HuR/ELAVL1,一种结合RNA中富含au元素的蛋白质。来自小鼠B淋巴瘤细胞的hhr敲除(KO) CH12细胞被发现具有较低的CSR和高突变效率,这是由于艾滋病依赖性DNA切割水平降低。HuR-KO CH12细胞没有表现出细胞周期和Myc表达的损伤,这在hur减少的脾B细胞中有报道。此外,清除活性氧(ROS)的药物不能挽救hr - ko CH12细胞中较低的CSR,这意味着ROS或c-Myc蛋白量的减少并不是hr - ko CH12细胞中CSR缺乏和高突变的原因。我们发现,在CH12细胞中,HuR与Top1 mRNA结合,完全缺失HuR可消除艾滋病依赖性的Top1蛋白合成抑制。此外,在hr - ko细胞中,CSR减少到IgG3是通过敲低Top1来挽救的,这表明消除艾滋病依赖性的Top1减少是hr - ko细胞中DNA切割效率低下、CSR和高突变的原因。这些结果表明,HuR是通过抑制Top1蛋白合成来调节艾滋病依赖性DNA切割,从而启动抗体多样化和获得性免疫所必需的。
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引用次数: 0
An update on studies characterizing adaptive immune responses in SARS-CoV-2 infection and COVID-19 vaccination. 关于 SARS-CoV-2 感染和 COVID-19 疫苗接种中适应性免疫反应特征的最新研究。
IF 4.8 4区 医学 Q2 IMMUNOLOGY Pub Date : 2023-08-07 DOI: 10.1093/intimm/dxad014
Ricardo da Silva Antunes, Alba Grifoni, April Frazier, Daniela Weiskopf, Alessandro Sette

In this brief opinion piece, we highlight our studies characterizing adaptive SARS-CoV-2 immune responses in infection and vaccination, and the ability of SARS-CoV-2-specific T cells to recognize emerging variants of concern, and the role of pre-existing cross-reactive T cells. In the context of the debate on correlates of protection, the pandemic's progression in the past 3 years underlined the need to consider how different adaptive immune responses might differentially contribute to protection from SARS-CoV-2 infection versus COVID-19 disease. Lastly, we discuss how cross-reactive T cell responses may be useful in generating a broad adaptive immunity, recognizing different variants and viral families. Considering vaccines with broadly conserved antigens could improve preparedness for future infectious disease outbreaks.

在这篇简短的评论文章中,我们重点介绍了我们的研究,这些研究描述了在感染和接种疫苗过程中 SARS-CoV-2 适应性免疫反应的特征、SARS-CoV-2 特异性 T 细胞识别新出现的相关变异体的能力以及原有交叉反应 T 细胞的作用。在关于保护相关性的讨论中,过去 3 年中大流行病的发展突显出有必要考虑不同的适应性免疫反应可能如何对 SARS-CoV-2 感染和 COVID-19 疾病的保护起到不同的作用。最后,我们讨论了交叉反应性 T 细胞反应如何有助于产生广泛的适应性免疫,识别不同的变体和病毒家族。考虑使用具有广泛保守抗原的疫苗可以提高对未来传染病爆发的防范能力。
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引用次数: 0
In This Issue 本期
IF 4.4 4区 医学 Q2 Medicine Pub Date : 2023-08-01 DOI: 10.1093/intimm/dxad020
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引用次数: 0
Zoobiquity experiments show the importance of the local MMP9-plasminogen axis in inflammatory bowel diseases in both dogs and patients. 动物biquity实验表明,局部mmp9 -纤溶酶原轴在犬和患者的炎症性肠病中的重要性。
IF 4.4 4区 医学 Q2 Medicine Pub Date : 2023-07-07 DOI: 10.1093/intimm/dxad006
Takeshi Yamasaki, Noriyuki Nagata, Toru Atsumi, Rie Hasebe, Yuki Tanaka, Izuru Ohki, Shimpei Kubota, Yuta Shinohara, Yong Bin Teoh, Nozomu Yokoyama, Noboru Sasaki, Kensuke Nakamura, Hiroshi Ohta, Takehiko Katsurada, Yoshihiro Matsuno, Shintaro Hojyo, Shigeru Hashimoto, Mitsuyoshi Takiguchi, Masaaki Murakami

Using a zoobiquity concept, we directly connect animal phenotypes to a human disease mechanism: the reduction of local plasminogen levels caused by matrix metalloproteinase-9 (MMP9) activity is associated with the development of inflammation in the intestines of dogs and patients with inflammatory bowel disease. We first investigated inflammatory colorectal polyps (ICRPs), which are a canine gastrointestinal disease characterized by the presence of idiopathic chronic inflammation, in Miniature Dachshund (MD) and found 31 missense disease-associated SNPs by whole-exome sequencing. We sequenced them in 10 other dog breeds and found five, PLG, TCOF1, TG, COL9A2 and COL4A4, only in MD. We then investigated two rare and breed-specific missense SNPs (T/T SNPs), PLG: c.477G > T and c.478A>T, and found that ICRPs with the T/T SNP risk alleles showed less intact plasminogen and plasmin activity in the lesions compared to ICRPs without the risk alleles but no differences in serum. Moreover, we show that MMP9, which is an NF-κB target, caused the plasminogen reduction and that intestinal epithelial cells expressing plasminogen molecules were co-localized with epithelial cells expressing MMP9 in normal colons with the risk alleles. Importantly, MMP9 expression in patients with ulcerous colitis or Crohn's disease also co-localized with epithelial cells showing enhanced NF-κB activation and less plasminogen expression. Overall, our zoobiquity experiments showed that MMP9 induces the plasminogen reduction in the intestine, contributing to the development of local inflammation and suggesting the local MMP9-plasminogen axis is a therapeutic target in both dogs and patients. Therefore, zoobiquity-type experiments could bring new perspectives for biomarkers and therapeutic targets.

利用动物异质性的概念,我们直接将动物表型与人类疾病机制联系起来:基质金属蛋白酶-9 (MMP9)活性引起的局部纤溶酶原水平的降低与狗和炎症性肠病患者肠道炎症的发展有关。我们首先研究了炎症性结肠直肠息肉(ICRPs),这是一种以特发性慢性炎症为特征的犬胃肠道疾病,在微型腊肠(MD)中,通过全外显子组测序发现了31个错义疾病相关的snp。我们在其他10个犬种中对它们进行了测序,发现只有在MD中有5个,分别是PLG、TCOF1、TG、COL9A2和COL4A4。然后我们研究了两个罕见且品种特异性的错义SNP (T/T SNP), PLG: c.477G >T和c.478A>T,发现与没有风险等位基因的icrp相比,具有T/T SNP风险等位基因的icrp在病变中显示出更少的完整的纤溶酶原和纤溶酶活性,但在血清中没有差异。此外,我们发现作为NF-κB靶点的MMP9导致纤溶酶原减少,并且在具有风险等位基因的正常结肠中,表达纤溶酶原分子的肠上皮细胞与表达MMP9的上皮细胞共定位。重要的是,溃疡性结肠炎或克罗恩病患者的MMP9表达也与上皮细胞共定位,表现出NF-κB活化增强和纤溶酶原表达减少。总的来说,我们的动物实验表明,MMP9诱导肠内纤溶酶原减少,促进局部炎症的发展,并表明局部MMP9-纤溶酶原轴是犬和患者的治疗靶点。因此,动物实验可以为生物标志物和治疗靶点提供新的视角。
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引用次数: 1
Correction to: IL-17 contributes to cardiac fibrosis following experimental autoimmune myocarditis by a PKCβ/Erk1/2/NF-κB-dependent signaling pathway. 修正:IL-17通过PKCβ/Erk1/2/NF-κ b依赖的信号通路参与实验性自身免疫性心肌炎后的心脏纤维化。
IF 4.4 4区 医学 Q2 Medicine Pub Date : 2023-07-07 DOI: 10.1093/intimm/dxac063
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引用次数: 0
Dupuytren's contracture-associated SNPs increase SFRP4 expression in non-immune cells including fibroblasts to enhance inflammation development. Dupuytren的收缩相关snp增加非免疫细胞(包括成纤维细胞)中SFRP4的表达,从而促进炎症的发展。
IF 4.4 4区 医学 Q2 Medicine Pub Date : 2023-07-07 DOI: 10.1093/intimm/dxad004
Hiroaki Kida, Jing-Jing Jiang, Yuichiro Matsui, Ikuko Takahashi, Rie Hasebe, Daisuke Kawamura, Takeshi Endo, Hiroki Shibayama, Makoto Kondo, Yasuhiko Nishio, Kinya Nishida, Yoshihiro Matsuno, Tsukasa Oikawa, Shimpei I Kubota, Shintaro Hojyo, Norimasa Iwasaki, Shigeru Hashimoto, Yuki Tanaka, Masaaki Murakami

Dupuytren's contracture (DC) is an inflammatory fibrosis characterized by fibroproliferative disorders of the palmar aponeurosis, for which there is no effective treatment. Although several genome-wide association studies have identified risk alleles associated with DC, the functional linkage between these alleles and the pathogenesis remains elusive. We here focused on two single nucleotide polymorphisms (SNPs) associated with DC, rs16879765 and rs17171229, in secreted frizzled related protein 4 (SFRP4). We investigated the association of SRFP4 with the IL-6 amplifier, which amplifies the production of IL-6, growth factors and chemokines in non-immune cells and aggravates inflammatory diseases via NF-κB enhancement. Knockdown of SFRP4 suppressed activation of the IL-6 amplifier in vitro and in vivo, whereas the overexpression of SFRP4 induced the activation of NF-κB-mediated transcription activity. Mechanistically, SFRP4 induced NF-κB activation by directly binding to molecules of the ubiquitination SFC complex, such as IkBα and βTrCP, followed by IkBα degradation. Furthermore, SFRP4 expression was significantly increased in fibroblasts derived from DC patients bearing the risk alleles. Consistently, fibroblasts with the risk alleles enhanced activation of the IL-6 amplifier. These findings indicate that the IL-6 amplifier is involved in the pathogenesis of DC, particularly in patients harboring the SFRP4 risk alleles. Therefore, SFRP4 is a potential therapeutic target for various inflammatory diseases and disorders, including DC.

Dupuytren's挛缩(DC)是一种以掌腱膜纤维增生性疾病为特征的炎性纤维化,目前尚无有效的治疗方法。尽管一些全基因组关联研究已经确定了与DC相关的风险等位基因,但这些等位基因与发病机制之间的功能联系仍然难以捉摸。我们在此重点研究了与DC相关的两个单核苷酸多态性(snp), rs16879765和rs17171229,在分泌卷曲相关蛋白4 (SFRP4)中。我们研究了SRFP4与IL-6放大器的关联,IL-6放大器放大非免疫细胞中IL-6、生长因子和趋化因子的产生,并通过NF-κB增强加重炎症性疾病。在体外和体内,敲低SFRP4可抑制IL-6放大器的激活,而过表达SFRP4可诱导NF-κ b介导的转录活性的激活。机制上,SFRP4通过直接结合泛素化SFC复合体分子,如IkBα和βTrCP,诱导NF-κB活化,随后IkBα降解。此外,在携带风险等位基因的DC患者的成纤维细胞中,SFRP4的表达显著增加。具有风险等位基因的成纤维细胞一致地增强了IL-6放大器的激活。这些发现表明,IL-6放大器参与了DC的发病机制,特别是在携带SFRP4风险等位基因的患者中。因此,SFRP4是包括DC在内的各种炎症性疾病的潜在治疗靶点。
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引用次数: 1
Induction of allograft tolerance by adoptive transfer of donor B cells: an immune regulatory strategy for transplantation using MHC-matched iPS cells. 供体B细胞过继移植诱导同种异体移植物耐受:mhc匹配iPS细胞移植的免疫调节策略
IF 4.4 4区 医学 Q2 Medicine Pub Date : 2023-07-07 DOI: 10.1093/intimm/dxad008
Tomoki Murata, Ryo Otsuka, Airi Sasaki, Tomoki Kamatani, Haruka Wada, Hisashi Yamakawa, Yoshinori Hasegawa, Ken-Ichiro Seino

For cellular or tissue transplantation using induced pluripotent stem cells (iPSCs), from the viewpoint of time and economic cost, the use of allogeneic ones is being considered. Immune regulation is one of the key issues in successful allogeneic transplantation. To reduce the risk of rejection, several attempts have been reported to eliminate effects of the major histocompatibility complex (MHC) on the iPSC-derived grafts. On the other hand, we have shown that minor antigen-induced rejection is not negligible even when the MHC's impact is mitigated. In organ transplantation, it is known that donor-specific transfusion (DST) can specifically control immune responses to the donor. However, whether DST could control the immune response in iPSC-based transplantation was not clarified. In this study, using a mouse skin transplantation model, we demonstrate that infusion of donor splenocytes can promote allograft tolerance in the MHC-matched but minor antigen-mismatched conditions. When narrowing down the cell types, we found that infusion of isolated splenic B cells was sufficient to control rejection. As a mechanism, the administration of donor B cells induced unresponsiveness but not deletion in recipient T cells, suggesting that the tolerance was induced in the periphery. The donor B cell transfusion induced allogeneic iPSC engraftment. These results suggest for the first time a possibility that DST using donor B cells could induce tolerance against allogeneic iPSC-derived grafts.

对于使用诱导多能干细胞(iPSCs)进行细胞或组织移植,从时间和经济成本的角度考虑,正在考虑使用同种异体干细胞。免疫调节是同种异体移植成功的关键问题之一。为了降低排斥反应的风险,已经报道了几种尝试来消除主要组织相容性复合体(MHC)对ipsc衍生移植物的影响。另一方面,我们已经证明,即使MHC的影响减轻了,轻微的抗原诱导的排斥反应也是不可忽视的。在器官移植中,已知供体特异性输血(DST)可以特异性地控制对供体的免疫反应。然而,DST是否能控制ipsc移植的免疫反应尚不清楚。在这项研究中,我们使用小鼠皮肤移植模型,证明在mhc匹配但抗原不匹配的情况下,输注供体脾细胞可以促进同种异体移植物的耐受性。当缩小细胞类型时,我们发现输注分离的脾B细胞足以控制排斥反应。作为一种机制,供体B细胞在受体T细胞中诱导无反应性而非缺失,这表明耐受性是在外周诱导的。供体B细胞输注诱导异基因iPSC移植。这些结果首次表明,使用供体B细胞的DST可能诱导对异体ipsc衍生移植物的耐受性。
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引用次数: 0
Fibronectin on target cells attenuates natural cytotoxicity of NK cells via myeloid immune checkpoint ILT3/LILRB4/gp49B. 靶细胞上的纤维连接蛋白通过骨髓免疫检查点ILT3/LILRB4/gp49B减弱NK细胞的天然细胞毒性。
IF 4.4 4区 医学 Q2 Medicine Pub Date : 2023-07-07 DOI: 10.1093/intimm/dxad012
Fumika Itagaki, Keita Nakatsuka, Haruka Sakai, Shota Endo, Mei-Tzu Su, Toshiyuki Takai

Natural killer (NK) cells play pivotal roles in innate immunity as well as in anti-tumor responses via natural killing, while their activity is tightly regulated by cell-surface inhibitory receptors. Immunoglobulin-like transcript 3/leukocyte immunoglobulin-like receptor B4 (ILT3/LILRB4, also known as gp49B in mice) is an inhibitory receptor expressed on activated NK cells as well as myeloid-lineage cells. The common physiologic ligand of human LILRB4 and gp49B was identified very recently as fibronectin, particularly the N-terminal 30 kDa domain (FN30). We hypothesized that LILRB4 could bind fibronectin on target cells in trans together with integrins, classical fibronectin receptors, in cis and deliver an inhibitory signal in NK cells, leading to attenuated natural killing. Flow cytometric and confocal microscopic analyses of NK cell-surface gp49B and integrins suggested that these novel and classical fibronectin receptors, respectively, co-engage fibronectin immobilized on a culture plate. Biochemical analyses indicated that tyrosine phosphorylation of spleen tyrosine kinase was augmented in gp49B-deficient NK cells upon binding to the immobilized fibronectin. While surface fibronectin-poor YAC-1 cells were evenly sensitive as to natural killing of both gp49B-positive and -negative NK cells, the killing of fibronectin-rich Lewis lung carcinoma cells, but not the FN30-knockout cells, was augmented among gp49B-deficient NK cells. These results suggest that the natural cytotoxicity of NK cells is negatively regulated through LILRB4/gp49B sensing fibronectin on target cells, which sheds light on the unexpected role of LILRB4 and fibronectin as a potential attenuator of NK cell cytotoxicity in the tumor microenvironment.

NK细胞通过自然杀伤在先天免疫和抗肿瘤反应中发挥关键作用,其活性受到细胞表面抑制受体的严格调控。免疫球蛋白样转录物3/白细胞免疫球蛋白样受体B4 (ILT3/LILRB4,在小鼠中也称为gp49B)是一种抑制受体,在活化的NK细胞和髓系细胞上表达。人类LILRB4和gp49B的共同生理配体是最近才确定的纤维连接蛋白,特别是n端30kda结构域(FN30)。我们假设LILRB4可以反式结合靶细胞上的纤维连接蛋白,与经典的纤维连接蛋白受体整合素顺式结合,并在NK细胞中传递抑制信号,导致自然杀伤减弱。NK细胞表面gp49B和整合素的流式细胞术和共聚焦显微镜分析表明,这些新型和经典的纤维连接蛋白受体分别与固定在培养板上的纤维连接蛋白共接合。生化分析表明,gp49b缺陷NK细胞与固定纤维连接蛋白结合后,脾脏酪氨酸激酶的酪氨酸磷酸化增强。虽然表面纤维连接蛋白缺乏的YAC-1细胞对gp49b阳性和阴性NK细胞的自然杀伤都很敏感,但在gp49b缺乏的NK细胞中,对富含纤维连接蛋白的Lewis肺癌细胞的杀伤能力增强,而对fn30敲除细胞的杀伤能力则没有增强。这些结果表明,NK细胞的天然细胞毒性通过LILRB4/gp49B感知靶细胞上的纤维连接蛋白而受到负调控,这揭示了LILRB4和纤维连接蛋白在肿瘤微环境中作为NK细胞毒性的潜在衰减剂的意想不到的作用。
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引用次数: 0
Exploring novel functions of BACH2 in the acquisition of antigen-specific antibodies. 探索BACH2在获得抗原特异性抗体中的新功能。
IF 4.4 4区 医学 Q2 Medicine Pub Date : 2023-05-19 DOI: 10.1093/intimm/dxac065
Kyoko Ochiai, Kazuhiko Igarashi

BACH2 [BTB (broad-complex, tramtrak and bric à brac) and CNC (cap 'n' collar) homolog 2] is known as a transcriptional repressor and broadly functions in regulating immune cell differentiation. Here, we focus on BACH2 function in B cells, where BACH2 was first shown to play an important role in the immune system. In B cells, BACH2 orchestrates the gene regulatory network that promotes class switch and affinity maturation of antibodies and simultaneously represses plasma-cell differentiation. In this context, BACH2 regulates gene expression by modulating chromatin organization, cooperatively with other transcription factors and chromatin regulators, such as IRF4 (interferon regulatory factor 4) and PC4 (positive coactivator 4), respectively. In addition, our recent observation raises the possibility that BACH2 has diverse functions, such as those in gene activation. Since dysfunction of BACH2 leads to the onset of human immune deficiencies, revealing new functions of BACH2 may give a cue to solve how BACH2 contributes to preventing these diseases.

BACH2 [BTB (broad-complex, tramtrak和bric - brac)和CNC (cap 'n' collar)同源物2]被认为是一种转录抑制因子,在调节免疫细胞分化方面具有广泛的功能。在这里,我们关注BACH2在B细胞中的功能,BACH2首次被证明在免疫系统中发挥重要作用。在B细胞中,BACH2协调基因调控网络,促进抗体的类别转换和亲和成熟,同时抑制浆细胞分化。在这种情况下,BACH2通过调节染色质组织来调节基因表达,并与其他转录因子和染色质调节剂如IRF4(干扰素调节因子4)和PC4(正辅激活因子4)合作。此外,我们最近的观察提出了BACH2具有多种功能的可能性,例如基因激活。由于BACH2的功能障碍导致人类免疫缺陷的发生,揭示BACH2的新功能可能为解决BACH2如何预防这些疾病提供线索。
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引用次数: 2
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International immunology
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