Pub Date : 2024-06-13DOI: 10.1038/s41423-024-01190-6
Qing Ouyang, Chao Wang, Tian Sang, Yan Tong, Jian Zhang, Yulan Chen, Xue Wang, Lingling Wu, Xu Wang, Ran Liu, Pu Chen, Jiaona Liu, Wanjun Shen, Zhe Feng, Li Zhang, Xuefeng Sun, Guangyan Cai, Li-Li Li, Xiangmei Chen
Managing renal fibrosis is challenging owing to the complex cell signaling redundancy in diseased kidneys. Renal fibrosis involves an immune response dominated by macrophages, which activates myofibroblasts in fibrotic niches. However, macrophages exhibit high heterogeneity, hindering their potential as therapeutic cell targets. Herein, we aimed to eliminate specific macrophage subsets that drive the profibrotic immune response in the kidney both temporally and spatially. We identified the major profibrotic macrophage subset (Fn1+Spp1+Arg1+) in the kidney and then constructed a 12-mer glycopeptide that was designated as bioactivated in vivo assembly PK (BIVA-PK) to deplete these cells. BIVA-PK specifically binds to and is internalized by profibrotic macrophages. By inducing macrophage cell death, BIVA-PK reshaped the renal microenvironment and suppressed profibrotic immune responses. The robust efficacy of BIVA-PK in ameliorating renal fibrosis and preserving kidney function highlights the value of targeting macrophage subsets as a potential therapy for patients with CKD.
{"title":"Depleting profibrotic macrophages using bioactivated in vivo assembly peptides ameliorates kidney fibrosis","authors":"Qing Ouyang, Chao Wang, Tian Sang, Yan Tong, Jian Zhang, Yulan Chen, Xue Wang, Lingling Wu, Xu Wang, Ran Liu, Pu Chen, Jiaona Liu, Wanjun Shen, Zhe Feng, Li Zhang, Xuefeng Sun, Guangyan Cai, Li-Li Li, Xiangmei Chen","doi":"10.1038/s41423-024-01190-6","DOIUrl":"10.1038/s41423-024-01190-6","url":null,"abstract":"Managing renal fibrosis is challenging owing to the complex cell signaling redundancy in diseased kidneys. Renal fibrosis involves an immune response dominated by macrophages, which activates myofibroblasts in fibrotic niches. However, macrophages exhibit high heterogeneity, hindering their potential as therapeutic cell targets. Herein, we aimed to eliminate specific macrophage subsets that drive the profibrotic immune response in the kidney both temporally and spatially. We identified the major profibrotic macrophage subset (Fn1+Spp1+Arg1+) in the kidney and then constructed a 12-mer glycopeptide that was designated as bioactivated in vivo assembly PK (BIVA-PK) to deplete these cells. BIVA-PK specifically binds to and is internalized by profibrotic macrophages. By inducing macrophage cell death, BIVA-PK reshaped the renal microenvironment and suppressed profibrotic immune responses. The robust efficacy of BIVA-PK in ameliorating renal fibrosis and preserving kidney function highlights the value of targeting macrophage subsets as a potential therapy for patients with CKD.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 8","pages":"826-841"},"PeriodicalIF":21.8,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The key role of structural cells in immune modulation has been revealed with the advent of single-cell multiomics, but the underlying mechanism remains poorly understood. Here, we revealed that the transcriptional activation of interferon regulatory factor 1 (IRF1) in response to ionizing radiation, cytotoxic chemicals and SARS-CoV-2 viral infection determines the fate of structural cells and regulates communication between structural and immune cells. Radiation-induced leakage of mtDNA initiates the nuclear translocation of IRF1, enabling it to regulate the transcription of inflammation- and cell death-related genes. Novel posttranslational modification (PTM) sites in the nuclear localization sequence (NLS) of IRF1 were identified. Functional analysis revealed that mutation of the acetylation site and the phosphorylation sites in the NLS blocked the transcriptional activation of IRF1 and reduced cell death in response to ionizing radiation. Mechanistically, reciprocal regulation between the single-stranded DNA sensors SSBP1 and IRF1, which restrains radiation-induced and STING/p300-mediated PTMs of IRF1, was revealed. In addition, genetic deletion or pharmacological inhibition of IRF1 tempered radiation-induced inflammatory cell death, and radiation mitigators also suppressed SARS-CoV-2 NSP-10-mediated activation of IRF1. Thus, we revealed a novel cytoplasm-oriented mechanism of IRF1 activation in structural cells that promotes inflammation and highlighted the potential effectiveness of IRF1 inhibitors against immune disorders.
{"title":"Chaperone- and PTM-mediated activation of IRF1 tames radiation-induced cell death and the inflammatory response","authors":"Fenghao Geng, Jianhui Chen, Bin Song, Zhicheng Tang, Xiaoqian Li, Shuaijun Zhang, Tingyi Yang, Yulan Liu, Wei Mo, Yining Zhang, Chuntang Sun, Lei Tan, Wenling Tu, Daojiang Yu, Jianping Cao, Shuyu Zhang","doi":"10.1038/s41423-024-01185-3","DOIUrl":"10.1038/s41423-024-01185-3","url":null,"abstract":"The key role of structural cells in immune modulation has been revealed with the advent of single-cell multiomics, but the underlying mechanism remains poorly understood. Here, we revealed that the transcriptional activation of interferon regulatory factor 1 (IRF1) in response to ionizing radiation, cytotoxic chemicals and SARS-CoV-2 viral infection determines the fate of structural cells and regulates communication between structural and immune cells. Radiation-induced leakage of mtDNA initiates the nuclear translocation of IRF1, enabling it to regulate the transcription of inflammation- and cell death-related genes. Novel posttranslational modification (PTM) sites in the nuclear localization sequence (NLS) of IRF1 were identified. Functional analysis revealed that mutation of the acetylation site and the phosphorylation sites in the NLS blocked the transcriptional activation of IRF1 and reduced cell death in response to ionizing radiation. Mechanistically, reciprocal regulation between the single-stranded DNA sensors SSBP1 and IRF1, which restrains radiation-induced and STING/p300-mediated PTMs of IRF1, was revealed. In addition, genetic deletion or pharmacological inhibition of IRF1 tempered radiation-induced inflammatory cell death, and radiation mitigators also suppressed SARS-CoV-2 NSP-10-mediated activation of IRF1. Thus, we revealed a novel cytoplasm-oriented mechanism of IRF1 activation in structural cells that promotes inflammation and highlighted the potential effectiveness of IRF1 inhibitors against immune disorders.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 8","pages":"856-872"},"PeriodicalIF":21.8,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141287824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-05DOI: 10.1038/s41423-024-01183-5
Akihiro Nakamura, Sungsin Jo, Sayaka Nakamura, Mansi K. Aparnathi, Shaghayegh Foroozan Boroojeni, Mariia Korshko, Ye-Soo Park, Himanshi Gupta, Sandra Vijayan, Jason S. Rockel, Mohit Kapoor, Igor Jurisica, Tae-Hwan Kim, Nigil Haroon
The hallmarks of spondyloarthritis (SpA) are type 3 immunity-driven inflammation and new bone formation (NBF). Macrophage migration inhibitory factor (MIF) was found to be a key driver of the pathogenesis of SpA by amplifying type 3 immunity, yet MIF-interacting molecules and networks remain elusive. Herein, we identified hypoxia-inducible factor-1 alpha (HIF1A) as an interacting partner molecule of MIF that drives SpA pathologies, including inflammation and NBF. HIF1A expression was increased in the joint tissues and synovial fluid of SpA patients and curdlan-injected SKG (curdlan-SKG) mice compared to the respective controls. Under hypoxic conditions in which HIF1A was stabilized, human and mouse neutrophils exhibited substantially increased expression of MIF and IL-23, an upstream type 3 immunity-related cytokine. Similar to MIF, systemic overexpression of IL-23 induced SpA pathology in SKG mice, while the injection of a HIF1A-selective inhibitor (PX-478) into curdlan-SKG mice prevented or attenuated SpA pathology, as indicated by a marked reduction in the expression of MIF and IL-23. Furthermore, genetic deletion of MIF or HIF1A inhibition with PX-478 in IL-23-overexpressing SKG mice did not induce evident arthritis or NBF, despite the presence of psoriasis-like dermatitis and blepharitis. We also found that MIF- and IL-23-expressing neutrophils infiltrated areas of the NBF in curdlan-SKG mice. These neutrophils potentially increased chondrogenesis and cell proliferation via the upregulation of STAT3 in periosteal cells and ligamental cells during endochondral ossification. Together, these results provide supporting evidence for an MIF/HIF1A regulatory network, and inhibition of HIF1A may be a novel therapeutic approach for SpA by suppressing type 3 immunity-mediated inflammation and NBF.
{"title":"HIF-1α and MIF enhance neutrophil-driven type 3 immunity and chondrogenesis in a murine spondyloarthritis model","authors":"Akihiro Nakamura, Sungsin Jo, Sayaka Nakamura, Mansi K. Aparnathi, Shaghayegh Foroozan Boroojeni, Mariia Korshko, Ye-Soo Park, Himanshi Gupta, Sandra Vijayan, Jason S. Rockel, Mohit Kapoor, Igor Jurisica, Tae-Hwan Kim, Nigil Haroon","doi":"10.1038/s41423-024-01183-5","DOIUrl":"10.1038/s41423-024-01183-5","url":null,"abstract":"The hallmarks of spondyloarthritis (SpA) are type 3 immunity-driven inflammation and new bone formation (NBF). Macrophage migration inhibitory factor (MIF) was found to be a key driver of the pathogenesis of SpA by amplifying type 3 immunity, yet MIF-interacting molecules and networks remain elusive. Herein, we identified hypoxia-inducible factor-1 alpha (HIF1A) as an interacting partner molecule of MIF that drives SpA pathologies, including inflammation and NBF. HIF1A expression was increased in the joint tissues and synovial fluid of SpA patients and curdlan-injected SKG (curdlan-SKG) mice compared to the respective controls. Under hypoxic conditions in which HIF1A was stabilized, human and mouse neutrophils exhibited substantially increased expression of MIF and IL-23, an upstream type 3 immunity-related cytokine. Similar to MIF, systemic overexpression of IL-23 induced SpA pathology in SKG mice, while the injection of a HIF1A-selective inhibitor (PX-478) into curdlan-SKG mice prevented or attenuated SpA pathology, as indicated by a marked reduction in the expression of MIF and IL-23. Furthermore, genetic deletion of MIF or HIF1A inhibition with PX-478 in IL-23-overexpressing SKG mice did not induce evident arthritis or NBF, despite the presence of psoriasis-like dermatitis and blepharitis. We also found that MIF- and IL-23-expressing neutrophils infiltrated areas of the NBF in curdlan-SKG mice. These neutrophils potentially increased chondrogenesis and cell proliferation via the upregulation of STAT3 in periosteal cells and ligamental cells during endochondral ossification. Together, these results provide supporting evidence for an MIF/HIF1A regulatory network, and inhibition of HIF1A may be a novel therapeutic approach for SpA by suppressing type 3 immunity-mediated inflammation and NBF.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 7","pages":"770-786"},"PeriodicalIF":21.8,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141255495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-05DOI: 10.1038/s41423-024-01180-8
Mario Ruiz Pérez, Christian Maueröder, Wolf Steels, Bruno Verstraeten, Sahine Lameire, Wei Xie, Laura Wyckaert, Jelle Huysentruyt, Tatyana Divert, Ria Roelandt, Amanda Gonçalves, Riet De Rycke, Kodi Ravichandran, Bart N. Lambrecht, Tom Taghon, Georges Leclercq, Peter Vandenabeele, Peter Tougaard
Acute systemic inflammation critically alters the function of the immune system, often promoting myelopoiesis at the expense of lymphopoiesis. In the thymus, systemic inflammation results in acute thymic atrophy and, consequently, impaired T-lymphopoiesis. The mechanism by which systemic inflammation impacts the thymus beyond suppressing T-cell development is still unclear. Here, we describe how the synergism between TL1A and IL-18 suppresses T-lymphopoiesis to promote thymic myelopoiesis. The protein levels of these two cytokines were elevated in the thymus during viral-induced thymus atrophy infection with murine cytomegalovirus (MCMV) or pneumonia virus of mice (PVM). In vivo administration of TL1A and IL-18 induced acute thymic atrophy, while thymic neutrophils expanded. Fate mapping with Ms4a3-Cre mice demonstrated that thymic neutrophils emerge from thymic granulocyte-monocyte progenitors (GMPs), while Rag1-Cre fate mapping revealed a common developmental path with lymphocytes. These effects could be modeled ex vivo using neonatal thymic organ cultures (NTOCs), where TL1A and IL-18 synergistically enhanced neutrophil production and egress. NOTCH blockade by the LY411575 inhibitor increased the number of neutrophils in the culture, indicating that NOTCH restricted steady-state thymic granulopoiesis. To promote myelopoiesis, TL1A, and IL-18 synergistically increased GM-CSF levels in the NTOC, which was mainly produced by thymic ILC1s. In support, TL1A- and IL-18-induced granulopoiesis was completely prevented in NTOCs derived from Csf2rb-/- mice and by GM-CSFR antibody blockade, revealing that GM-CSF is the essential factor driving thymic granulopoiesis. Taken together, our findings reveal that TL1A and IL-18 synergism induce acute thymus atrophy while promoting extramedullary thymic granulopoiesis in a NOTCH and GM-CSF-controlled manner.
急性全身性炎症会严重改变免疫系统的功能，通常会促进骨髓造血，而牺牲淋巴造血。在胸腺中，全身性炎症会导致急性胸腺萎缩，从而损害 T 淋巴细胞的生成。除了抑制 T 细胞发育外，全身性炎症影响胸腺的机制仍不清楚。在这里，我们描述了TL1A和IL-18如何协同抑制T淋巴细胞生成以促进胸腺骨髓细胞生成。在病毒诱导的胸腺萎缩感染小鼠巨细胞病毒（MCMV）或小鼠肺炎病毒（PVM）期间，胸腺中这两种细胞因子的蛋白水平升高。体内注射TL1A和IL-18会诱发急性胸腺萎缩，同时胸腺中性粒细胞会增大。用Ms4a3-Cre小鼠绘制的命运图谱显示，胸腺中性粒细胞是从胸腺粒细胞-单核细胞祖细胞（GMPs）中产生的，而Rag1-Cre命运图谱则显示了与淋巴细胞共同的发育路径。这些效应可通过新生儿胸腺器官培养物（NTOCs）进行体内外模拟，其中TL1A和IL-18协同增强了中性粒细胞的产生和排出。LY411575抑制剂阻断NOTCH可增加培养物中中性粒细胞的数量，这表明NOTCH限制了稳态胸腺粒细胞生成。为促进骨髓造血，TL1A 和 IL-18 协同提高了 NTOC 中 GM-CSF 的水平，而 GM-CSF 主要由胸腺 ILC1s 产生。此外，TL1A和IL-18诱导的粒细胞生成在Csf2rb-/-小鼠的NTOC中和GM-CSFR抗体阻断后完全被阻止，这表明GM-CSF是驱动胸腺粒细胞生成的重要因子。综上所述，我们的研究结果表明，TL1A和IL-18协同诱导急性胸腺萎缩，同时以NOTCH和GM-CSF控制的方式促进髓外胸腺造粒。
{"title":"TL1A and IL-18 synergy promotes GM-CSF-dependent thymic granulopoiesis in mice","authors":"Mario Ruiz Pérez, Christian Maueröder, Wolf Steels, Bruno Verstraeten, Sahine Lameire, Wei Xie, Laura Wyckaert, Jelle Huysentruyt, Tatyana Divert, Ria Roelandt, Amanda Gonçalves, Riet De Rycke, Kodi Ravichandran, Bart N. Lambrecht, Tom Taghon, Georges Leclercq, Peter Vandenabeele, Peter Tougaard","doi":"10.1038/s41423-024-01180-8","DOIUrl":"10.1038/s41423-024-01180-8","url":null,"abstract":"Acute systemic inflammation critically alters the function of the immune system, often promoting myelopoiesis at the expense of lymphopoiesis. In the thymus, systemic inflammation results in acute thymic atrophy and, consequently, impaired T-lymphopoiesis. The mechanism by which systemic inflammation impacts the thymus beyond suppressing T-cell development is still unclear. Here, we describe how the synergism between TL1A and IL-18 suppresses T-lymphopoiesis to promote thymic myelopoiesis. The protein levels of these two cytokines were elevated in the thymus during viral-induced thymus atrophy infection with murine cytomegalovirus (MCMV) or pneumonia virus of mice (PVM). In vivo administration of TL1A and IL-18 induced acute thymic atrophy, while thymic neutrophils expanded. Fate mapping with Ms4a3-Cre mice demonstrated that thymic neutrophils emerge from thymic granulocyte-monocyte progenitors (GMPs), while Rag1-Cre fate mapping revealed a common developmental path with lymphocytes. These effects could be modeled ex vivo using neonatal thymic organ cultures (NTOCs), where TL1A and IL-18 synergistically enhanced neutrophil production and egress. NOTCH blockade by the LY411575 inhibitor increased the number of neutrophils in the culture, indicating that NOTCH restricted steady-state thymic granulopoiesis. To promote myelopoiesis, TL1A, and IL-18 synergistically increased GM-CSF levels in the NTOC, which was mainly produced by thymic ILC1s. In support, TL1A- and IL-18-induced granulopoiesis was completely prevented in NTOCs derived from Csf2rb-/- mice and by GM-CSFR antibody blockade, revealing that GM-CSF is the essential factor driving thymic granulopoiesis. Taken together, our findings reveal that TL1A and IL-18 synergism induce acute thymus atrophy while promoting extramedullary thymic granulopoiesis in a NOTCH and GM-CSF-controlled manner.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 8","pages":"807-825"},"PeriodicalIF":21.8,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01180-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141255646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-31DOI: 10.1038/s41423-024-01168-4
Yufang Shi, Andreas Strasser, Douglas R. Green, Eicke Latz, Alberto Mantovani, Gerry Melino
{"title":"Legacy of the discovery of the T-cell receptor: 40 years of shaping basic immunology and translational work to develop novel therapies","authors":"Yufang Shi, Andreas Strasser, Douglas R. Green, Eicke Latz, Alberto Mantovani, Gerry Melino","doi":"10.1038/s41423-024-01168-4","DOIUrl":"10.1038/s41423-024-01168-4","url":null,"abstract":"","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 7","pages":"790-797"},"PeriodicalIF":21.8,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141183467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The development of distinct dendritic cell (DC) subsets, namely, plasmacytoid DCs (pDCs) and conventional DC subsets (cDC1s and cDC2s), is controlled by specific transcription factors. IRF8 is essential for the fate specification of cDC1s. However, how the expression of Irf8 is regulated is not fully understood. In this study, we identified TRIM33 as a critical regulator of DC differentiation and maintenance. TRIM33 deletion in Trim33fl/fl Cre-ERT2 mice significantly impaired DC differentiation from hematopoietic progenitors at different developmental stages. TRIM33 deficiency downregulated the expression of multiple genes associated with DC differentiation in these progenitors. TRIM33 promoted the transcription of Irf8 to facilitate the differentiation of cDC1s by maintaining adequate CDK9 and Ser2 phosphorylated RNA polymerase II (S2 Pol II) levels at Irf8 gene sites. Moreover, TRIM33 prevented the apoptosis of DCs and progenitors by directly suppressing the PU.1-mediated transcription of Bcl2l11, thereby maintaining DC homeostasis. Taken together, our findings identified TRIM33 as a novel and crucial regulator of DC differentiation and maintenance through the modulation of Irf8 and Bcl2l11 expression. The finding that TRIM33 functions as a critical regulator of both DC differentiation and survival provides potential benefits for devising DC-based immune interventions and therapies.
{"title":"TRIM33 plays a critical role in regulating dendritic cell differentiation and homeostasis by modulating Irf8 and Bcl2l11 transcription","authors":"Xiangyi Shen, Xiaoguang Li, Tao Wu, Tingting Guo, Jiaoyan Lv, Zhimin He, Maocai Luo, Xinyi Zhu, Yujie Tian, Wenlong Lai, Chen Dong, Xiaoyu Hu, Li Wu","doi":"10.1038/s41423-024-01179-1","DOIUrl":"10.1038/s41423-024-01179-1","url":null,"abstract":"The development of distinct dendritic cell (DC) subsets, namely, plasmacytoid DCs (pDCs) and conventional DC subsets (cDC1s and cDC2s), is controlled by specific transcription factors. IRF8 is essential for the fate specification of cDC1s. However, how the expression of Irf8 is regulated is not fully understood. In this study, we identified TRIM33 as a critical regulator of DC differentiation and maintenance. TRIM33 deletion in Trim33fl/fl Cre-ERT2 mice significantly impaired DC differentiation from hematopoietic progenitors at different developmental stages. TRIM33 deficiency downregulated the expression of multiple genes associated with DC differentiation in these progenitors. TRIM33 promoted the transcription of Irf8 to facilitate the differentiation of cDC1s by maintaining adequate CDK9 and Ser2 phosphorylated RNA polymerase II (S2 Pol II) levels at Irf8 gene sites. Moreover, TRIM33 prevented the apoptosis of DCs and progenitors by directly suppressing the PU.1-mediated transcription of Bcl2l11, thereby maintaining DC homeostasis. Taken together, our findings identified TRIM33 as a novel and crucial regulator of DC differentiation and maintenance through the modulation of Irf8 and Bcl2l11 expression. The finding that TRIM33 functions as a critical regulator of both DC differentiation and survival provides potential benefits for devising DC-based immune interventions and therapies.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 7","pages":"752-769"},"PeriodicalIF":21.8,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11214632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141183434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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