Undergraduate courses in immunology are content-heavy and combined with a new, complex vocabulary, can be an overwhelming subject for students. In-class active learning approaches have been found to improve understanding of difficult concepts in science, technology, engineering and mathematics (STEM) disciplines; however, many undergraduate courses maintain a high dependence on lecture-style teaching because of time constraints, content demands and student resistance. We designed an online, out-of-class activity, the "Life and Death of a T cell", to complement a lecture on a complex immunological concept, T-cell development. Inspired by the "Choose Your Own Adventure" children's books, a fictional narrative was created in which students assume the role of a cell with a dream of becoming a helper T cell. Decision-making scenarios then prompt students to draw on their knowledge from the lecture to successfully navigate the steps of T-cell development. The activity was built on two platforms, Google Forms and H5P (HTML 5 Package), both of which are readily accessible and allow the inclusion of branching logic and the creation of a decision tree-based activity. An anonymous survey revealed that students found this interactive approach enjoyable, and their perceived understanding of the content significantly increased. Students appreciated the inclusion of a novel learning resource, with requests for similar activities to be developed for other immunological concepts. In conclusion, we developed a narrative-based, decision-making activity to complement a lecture on T-cell development. As an out-of-class activity, this style of learning approach can potentially capitalize on the benefits of active learning, while also overcoming barriers of student resistance.
免疫学本科课程内容繁杂,再加上新的、复杂的词汇,对学生来说可能是一门难以承受的学科。研究发现,课内主动学习方法可以提高学生对科学、技术、工程和数学(STEM)学科中困难概念的理解;然而,由于时间限制、内容要求和学生的抵触情绪,许多本科课程仍然高度依赖讲授式教学。我们设计了一个名为 "T 细胞的生与死 "的在线课外活动,以补充关于 T 细胞发育这一复杂免疫学概念的讲座。受 "选择你自己的冒险"(Choose Your Own Adventure)儿童读物的启发,我们设计了一个虚构的故事,让学生扮演一个梦想成为辅助性 T 细胞的细胞。然后,决策情景会促使学生利用讲座中的知识成功完成 T 细胞发育的各个步骤。该活动建立在两个平台上:Google Forms 和 H5P(HTML 5 软件包),这两个平台都很容易访问,并允许加入分支逻辑和创建基于决策树的活动。一项匿名调查显示,学生们认为这种互动方法很有趣,而且他们对教学内容的理解能力明显提高。学生们对这种新颖的学习资源表示赞赏,并要求为其他免疫学概念开发类似的活动。总之,我们开发了一种基于叙事的决策活动,以补充有关 T 细胞发育的讲座。作为一种课外活动,这种学习方式既能发挥主动学习的优势,又能克服学生的抵触情绪。
{"title":"Choose your own T-cell fate: creation of a narrative-based, decision-making activity to engage students in immunology.","authors":"Helen E Ritchie, Gareth Denyer, Kylie E Webster","doi":"10.1111/imcb.12833","DOIUrl":"https://doi.org/10.1111/imcb.12833","url":null,"abstract":"<p><p>Undergraduate courses in immunology are content-heavy and combined with a new, complex vocabulary, can be an overwhelming subject for students. In-class active learning approaches have been found to improve understanding of difficult concepts in science, technology, engineering and mathematics (STEM) disciplines; however, many undergraduate courses maintain a high dependence on lecture-style teaching because of time constraints, content demands and student resistance. We designed an online, out-of-class activity, the \"Life and Death of a T cell\", to complement a lecture on a complex immunological concept, T-cell development. Inspired by the \"Choose Your Own Adventure\" children's books, a fictional narrative was created in which students assume the role of a cell with a dream of becoming a helper T cell. Decision-making scenarios then prompt students to draw on their knowledge from the lecture to successfully navigate the steps of T-cell development. The activity was built on two platforms, Google Forms and H5P (HTML 5 Package), both of which are readily accessible and allow the inclusion of branching logic and the creation of a decision tree-based activity. An anonymous survey revealed that students found this interactive approach enjoyable, and their perceived understanding of the content significantly increased. Students appreciated the inclusion of a novel learning resource, with requests for similar activities to be developed for other immunological concepts. In conclusion, we developed a narrative-based, decision-making activity to complement a lecture on T-cell development. As an out-of-class activity, this style of learning approach can potentially capitalize on the benefits of active learning, while also overcoming barriers of student resistance.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581419","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}
Arman Safavi, Jerome Samir, Mandeep Singh, Martina Bonomi, Raymond Yip Louie, Kenneth Micklethwaite, Fabio Luciani
Anti-CD19 Chimeric Antigen Receptor (CAR)-T cell therapies have shown promise for treating B cell malignancies, but the clinical outcome is influenced by both the CAR-T product and the patient's immune system. The role of γδ T cells in the context of CAR-T cell therapy remains poorly understood. This study investigates the transcriptional heterogeneity, clonal expansion and dynamics of γδ T cells in patients undergoing anti-CD19 CAR-T cell therapy. Longitudinal single cell multi-omics analysis was performed on γδ T cells from four patients receiving anti-CD19 CAR-T cell therapy. Single cell RNA-seq, antibody-based protein profiling (AbSeq) and full-length TCRγδ sequences revealed clonally expanded populations displaying plasticity in T cell differentiation, and temporal dynamics of large clones, suggesting ongoing expansion and differentiation. Clonally expanded γδ T cells had heterogeneous gene expression profiles, occupying seven transcriptionally distinct clusters. Analysis of chemokine markers indicated cluster-specific homing tendencies of circulating γδ T cells to peripheral tissues. We found unexpectedly high frequencies of Vδ1 and Vδ3 cells in the blood with distinct gene and protein expression profiles. This analysis provides insights into the dynamic and heterogeneous nature of γδ T cells following anti-CD19 CAR-T cell therapy, contributing valuable information for optimizing CAR-T cell therapies in B cell malignancies.
抗CD19嵌合抗原受体(CAR)-T细胞疗法已显示出治疗B细胞恶性肿瘤的前景,但临床结果受CAR-T产品和患者免疫系统的影响。γδT细胞在CAR-T细胞疗法中的作用仍鲜为人知。本研究调查了接受抗CD19 CAR-T细胞治疗的患者体内γδT细胞的转录异质性、克隆扩增和动态变化。对接受抗 CD19 CAR-T 细胞疗法的四名患者的 γδ T 细胞进行了纵向单细胞多组学分析。单细胞 RNA-seq、基于抗体的蛋白质分析(AbSeq)和全长 TCRγδ 序列揭示了克隆扩增的群体,显示了 T 细胞分化的可塑性,以及大克隆的时间动态性,表明了持续的扩增和分化。克隆扩增的γδT细胞具有异质性基因表达谱,占据了七个转录不同的集群。趋化因子标记物的分析表明,循环中的γδT细胞具有向外周组织归巢的特异性集群倾向。我们意外地发现,血液中的 Vδ1 和 Vδ3 细胞频率很高,而且基因和蛋白表达谱截然不同。这项分析深入揭示了抗CD19 CAR-T细胞疗法后γδT细胞的动态和异质性,为优化B细胞恶性肿瘤的CAR-T细胞疗法提供了有价值的信息。
{"title":"Identification of clonally expanded γδ T-cell populations during CAR-T cell therapy.","authors":"Arman Safavi, Jerome Samir, Mandeep Singh, Martina Bonomi, Raymond Yip Louie, Kenneth Micklethwaite, Fabio Luciani","doi":"10.1111/imcb.12834","DOIUrl":"https://doi.org/10.1111/imcb.12834","url":null,"abstract":"<p><p>Anti-CD19 Chimeric Antigen Receptor (CAR)-T cell therapies have shown promise for treating B cell malignancies, but the clinical outcome is influenced by both the CAR-T product and the patient's immune system. The role of γδ T cells in the context of CAR-T cell therapy remains poorly understood. This study investigates the transcriptional heterogeneity, clonal expansion and dynamics of γδ T cells in patients undergoing anti-CD19 CAR-T cell therapy. Longitudinal single cell multi-omics analysis was performed on γδ T cells from four patients receiving anti-CD19 CAR-T cell therapy. Single cell RNA-seq, antibody-based protein profiling (AbSeq) and full-length TCRγδ sequences revealed clonally expanded populations displaying plasticity in T cell differentiation, and temporal dynamics of large clones, suggesting ongoing expansion and differentiation. Clonally expanded γδ T cells had heterogeneous gene expression profiles, occupying seven transcriptionally distinct clusters. Analysis of chemokine markers indicated cluster-specific homing tendencies of circulating γδ T cells to peripheral tissues. We found unexpectedly high frequencies of Vδ1 and Vδ3 cells in the blood with distinct gene and protein expression profiles. This analysis provides insights into the dynamic and heterogeneous nature of γδ T cells following anti-CD19 CAR-T cell therapy, contributing valuable information for optimizing CAR-T cell therapies in B cell malignancies.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581421","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}
Pub Date : 2024-11-01Epub Date: 2024-09-24DOI: 10.1111/imcb.12823
Anne-Marie Aubin, Daria Vdovenko, Roxanne Collin, Lois Balmer, Lise Coderre, Grant Morahan, Félix Lombard-Vadnais, Sylvie Lesage
The humoral response is complex and involves multiple cellular populations and signaling pathways. Bacterial and viral infections, as well as immunization regimens, can trigger this type of response, promoting the formation of microanatomical cellular structures called germinal centers (GCs). GCs formed in secondary lymphoid organs support the differentiation of high-affinity plasma cells and memory B cells. There is growing evidence that the quality of the humoral response is influenced by genetic variants. Using 12 genetically divergent mouse strains, we assessed the impact of genetics on GC cellular traits. At steady state, in the spleen, lymph nodes and Peyer's patches, we quantified GC B cells, plasma cells and follicular helper T cells. These traits were also quantified in the spleen of mice following immunization with a foreign antigen, namely, sheep red blood cells, in addition to the number and size of GCs. We observed both strain- and organ-specific variations in cell type abundance, as well as for GC number and size. Moreover, we find that some of these traits are highly heritable. Importantly, the results of this study inform on the impact of genetic diversity in shaping the GC response and identify the traits that are the most impacted by genetic background.
{"title":"Variations in the germinal center response revealed by genetically diverse mouse strains.","authors":"Anne-Marie Aubin, Daria Vdovenko, Roxanne Collin, Lois Balmer, Lise Coderre, Grant Morahan, Félix Lombard-Vadnais, Sylvie Lesage","doi":"10.1111/imcb.12823","DOIUrl":"10.1111/imcb.12823","url":null,"abstract":"<p><p>The humoral response is complex and involves multiple cellular populations and signaling pathways. Bacterial and viral infections, as well as immunization regimens, can trigger this type of response, promoting the formation of microanatomical cellular structures called germinal centers (GCs). GCs formed in secondary lymphoid organs support the differentiation of high-affinity plasma cells and memory B cells. There is growing evidence that the quality of the humoral response is influenced by genetic variants. Using 12 genetically divergent mouse strains, we assessed the impact of genetics on GC cellular traits. At steady state, in the spleen, lymph nodes and Peyer's patches, we quantified GC B cells, plasma cells and follicular helper T cells. These traits were also quantified in the spleen of mice following immunization with a foreign antigen, namely, sheep red blood cells, in addition to the number and size of GCs. We observed both strain- and organ-specific variations in cell type abundance, as well as for GC number and size. Moreover, we find that some of these traits are highly heritable. Importantly, the results of this study inform on the impact of genetic diversity in shaping the GC response and identify the traits that are the most impacted by genetic background.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337947","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}
Pub Date : 2024-11-01Epub Date: 2024-10-13DOI: 10.1111/imcb.12825
Ting He, Kangzhi Chen, Qian Zhou, Haobing Cai, Huan Yang
Myasthenia gravis (MG) is the most frequent immune-mediated neurological disorder, characterized by fluctuating muscle weakness. Specific recognition of self-antigens by T-cell receptors (TCRs) and B-cell receptors (BCRs), coupled with T-B cell interactions, activates B cells to produce autoantibodies, which are critical for the initiation and perpetuation of MG. The immune repertoire comprises all functionally diverse T and B cells at a specific time point in an individual, reflecting the essence of immune selectivity. By sequencing the nucleotide sequences of TCRs and BCRs, it is possible to track individual T- and B-cell clones. This review delves into the generation of autoreactive TCRs and BCRs in MG and comprehensively examines the applications of immune repertoire sequencing in understanding disease pathogenesis, developing diagnostic and prognostic markers and informing targeted therapies. We also discuss the current limitations and future potential of this approach.
重症肌无力(MG)是最常见的免疫介导的神经系统疾病,以波动性肌无力为特征。T细胞受体(TCR)和B细胞受体(BCR)对自身抗原的特异性识别,加上T-B细胞的相互作用,激活B细胞产生自身抗体,这对肌无力症的发生和持续至关重要。免疫复合物包括个体在特定时间点的所有功能各异的 T 细胞和 B 细胞,反映了免疫选择性的本质。通过对 TCR 和 BCR 的核苷酸序列进行测序,可以追踪单个 T 细胞和 B 细胞克隆。这篇综述深入探讨了 MG 中自身反应性 TCR 和 BCR 的产生,并全面探讨了免疫复合物测序在了解疾病发病机制、开发诊断和预后标记物以及为靶向治疗提供信息方面的应用。我们还讨论了这种方法目前的局限性和未来的潜力。
{"title":"Immune repertoire profiling in myasthenia gravis.","authors":"Ting He, Kangzhi Chen, Qian Zhou, Haobing Cai, Huan Yang","doi":"10.1111/imcb.12825","DOIUrl":"10.1111/imcb.12825","url":null,"abstract":"<p><p>Myasthenia gravis (MG) is the most frequent immune-mediated neurological disorder, characterized by fluctuating muscle weakness. Specific recognition of self-antigens by T-cell receptors (TCRs) and B-cell receptors (BCRs), coupled with T-B cell interactions, activates B cells to produce autoantibodies, which are critical for the initiation and perpetuation of MG. The immune repertoire comprises all functionally diverse T and B cells at a specific time point in an individual, reflecting the essence of immune selectivity. By sequencing the nucleotide sequences of TCRs and BCRs, it is possible to track individual T- and B-cell clones. This review delves into the generation of autoreactive TCRs and BCRs in MG and comprehensively examines the applications of immune repertoire sequencing in understanding disease pathogenesis, developing diagnostic and prognostic markers and informing targeted therapies. We also discuss the current limitations and future potential of this approach.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454136","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}
Pub Date : 2024-11-01Epub Date: 2024-10-30DOI: 10.1111/imcb.12829
Nathan J Mackenzie, Kate Zimmermann, Clarissa Nicholls, Mahasha Pj Perera, Alexander Ngoo, Penny L Jeffery, Ian Vela, Tony J Kenna, Elizabeth D Williams, Patrick B Thomas
Treatments targeting the immune system only benefit a subset of patients with bladder cancer (BC). Biomarkers predictive of BC progression and response to specific therapeutic interventions are required. We evaluated whether peripheral blood immune subsets and expression of clinically relevant immune checkpoint markers are associated with clinicopathologic features of BC. Peripheral blood mononuclear cells isolated from blood collected from 23 patients with BC and 9 age-matched unaffected-by-cancer control donors were assessed using a 21-parameter flow cytometry panel composed of markers of T, B, natural killer and myeloid populations and immune checkpoint markers. Patients with BC had significantly lower numbers of circulating CD19+ B cells and elevated circulating CD4+CD8+ T cells compared with the control cohort. Immune checkpoint markers programmed cell death protein 1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) were elevated in the total peripheral immune cell population in patients with BC. Within the BC cohort, PD-1 expression in T and myeloid cells was elevated in muscle-invasive compared with non-muscle-invasive disease. In addition, elevated T, B and myeloid PD-1 cell surface expression was significantly associated with tumor stage, suggesting that measures of peripheral immune cell exhaustion may be a predictor of tumor progression in BC. Finally, positive correlations between expression levels of the various immune checkpoints both overall and within key peripheral blood immune subsets collected from patients with BC were observed, highlighting likely coregulation of peripheral immune checkpoint expression. The peripheral blood immunophenotype in patients with BC is altered compared with cancer-free individuals. Understanding this dysregulated immune profile will contribute to the identification of diagnostic and prognostic indicators to guide effective immune-targeted, personalized treatments.
针对免疫系统的治疗只能使一部分膀胱癌(BC)患者受益。需要能预测膀胱癌进展和对特定治疗干预反应的生物标志物。我们评估了外周血免疫亚群和临床相关免疫检查点标记物的表达是否与膀胱癌的临床病理特征相关。从 23 名 BC 患者和 9 名年龄匹配的未受癌症影响的对照供血者的血液中分离出外周血单核细胞,使用 21 个参数的流式细胞仪面板进行评估,该面板由 T、B、自然杀伤细胞、髓样细胞群标记物和免疫检查点标记物组成。与对照组相比,BC 患者的循环 CD19+ B 细胞数量明显减少,而循环 CD4+CD8+ T 细胞数量增加。免疫检查点标记物程序性细胞死亡蛋白1(PD-1)和T细胞免疫球蛋白和含粘蛋白域-3(TIM-3)在BC患者的外周免疫细胞总数中升高。在 BC 患者群中,肌肉浸润性疾病的 T 细胞和骨髓细胞中 PD-1 的表达高于非肌肉浸润性疾病。此外,T、B和髓系PD-1细胞表面表达的升高与肿瘤分期显著相关,这表明外周免疫细胞衰竭的测量值可能是预测BC肿瘤进展的一个指标。最后,从 BC 患者采集的外周血免疫亚群中观察到,各种免疫检查点的表达水平在整体上和关键亚群中都呈正相关,这表明外周血免疫检查点的表达可能存在核心关联。与未患癌症的人相比,BC 患者的外周血免疫表型发生了改变。了解这种失调的免疫特征将有助于确定诊断和预后指标,从而指导有效的免疫靶向个性化治疗。
{"title":"Altered immunophenotypic expression in the peripheral bladder cancer immune landscape.","authors":"Nathan J Mackenzie, Kate Zimmermann, Clarissa Nicholls, Mahasha Pj Perera, Alexander Ngoo, Penny L Jeffery, Ian Vela, Tony J Kenna, Elizabeth D Williams, Patrick B Thomas","doi":"10.1111/imcb.12829","DOIUrl":"10.1111/imcb.12829","url":null,"abstract":"<p><p>Treatments targeting the immune system only benefit a subset of patients with bladder cancer (BC). Biomarkers predictive of BC progression and response to specific therapeutic interventions are required. We evaluated whether peripheral blood immune subsets and expression of clinically relevant immune checkpoint markers are associated with clinicopathologic features of BC. Peripheral blood mononuclear cells isolated from blood collected from 23 patients with BC and 9 age-matched unaffected-by-cancer control donors were assessed using a 21-parameter flow cytometry panel composed of markers of T, B, natural killer and myeloid populations and immune checkpoint markers. Patients with BC had significantly lower numbers of circulating CD19<sup>+</sup> B cells and elevated circulating CD4<sup>+</sup>CD8<sup>+</sup> T cells compared with the control cohort. Immune checkpoint markers programmed cell death protein 1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) were elevated in the total peripheral immune cell population in patients with BC. Within the BC cohort, PD-1 expression in T and myeloid cells was elevated in muscle-invasive compared with non-muscle-invasive disease. In addition, elevated T, B and myeloid PD-1 cell surface expression was significantly associated with tumor stage, suggesting that measures of peripheral immune cell exhaustion may be a predictor of tumor progression in BC. Finally, positive correlations between expression levels of the various immune checkpoints both overall and within key peripheral blood immune subsets collected from patients with BC were observed, highlighting likely coregulation of peripheral immune checkpoint expression. The peripheral blood immunophenotype in patients with BC is altered compared with cancer-free individuals. Understanding this dysregulated immune profile will contribute to the identification of diagnostic and prognostic indicators to guide effective immune-targeted, personalized treatments.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542356","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}
Pub Date : 2024-11-01Epub Date: 2024-10-08DOI: 10.1111/imcb.12824
Colin Guth, Nathachit Limjunyawong, Priyanka Pundir
Chronic wounds significantly burden health care systems worldwide, requiring novel strategies to ease their impact. Many physiological processes underlying wound healing are well studied but the role of mast cells remains controversial. Mast cells are innate immune cells and play an essential role in barrier function by inducing inflammation to defend the host against chemical irritants and infections, among others. Many mast cell-derived mediators have proposed roles in wound healing; however, in vivo evidence using mouse models has produced conflicting results. Recently, studies involving more complex wound models such as infected wounds, diabetic wounds and wounds healing under psychological stress suggest that mast cells play critical roles in these processes. This review briefly summarizes the existing literature regarding mast cells in normal wounds and the potential reasons for the contradictory results. Focus will be placed on examining more recent work emerging in the last 5 years that explores mast cells in more complex systems of wound healing, including infection, psychological stress and diabetes, with a discussion of how these discoveries may inspire future work in the field.
{"title":"The evolving role of mast cells in wound healing: insights from recent research and diverse models.","authors":"Colin Guth, Nathachit Limjunyawong, Priyanka Pundir","doi":"10.1111/imcb.12824","DOIUrl":"10.1111/imcb.12824","url":null,"abstract":"<p><p>Chronic wounds significantly burden health care systems worldwide, requiring novel strategies to ease their impact. Many physiological processes underlying wound healing are well studied but the role of mast cells remains controversial. Mast cells are innate immune cells and play an essential role in barrier function by inducing inflammation to defend the host against chemical irritants and infections, among others. Many mast cell-derived mediators have proposed roles in wound healing; however, in vivo evidence using mouse models has produced conflicting results. Recently, studies involving more complex wound models such as infected wounds, diabetic wounds and wounds healing under psychological stress suggest that mast cells play critical roles in these processes. This review briefly summarizes the existing literature regarding mast cells in normal wounds and the potential reasons for the contradictory results. Focus will be placed on examining more recent work emerging in the last 5 years that explores mast cells in more complex systems of wound healing, including infection, psychological stress and diabetes, with a discussion of how these discoveries may inspire future work in the field.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386737","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}
Pub Date : 2024-11-01Epub Date: 2024-10-17DOI: 10.1111/imcb.12826
Ahmed Me Abdalla, Yu Miao, Ning Ming, Chenxi Ouyang
T-cell-mediated therapeutic strategies are the most potent effectors of cancer immunotherapy. However, an essential barrier to this therapy in solid tumors is disrupting the anti-cancer immune response, cancer-immunity cycle, T-cell priming, trafficking and T-cell cytotoxic capacity. Thus, reinforcing the anti-cancer immune response is needed to improve the effectiveness of T-cell-mediated therapy. Tumor-associated protease ADAM10, endothelial cells (ECs) and cytotoxic CD8+ T cells engage in complex communication via adhesion, transmigration and chemotactic mechanisms to facilitate an anti-cancer immune response. The precise impact of ADAM10 on the intricate mechanisms underlying these interactions remains unclear. This paper broadly explores how ADAM10, through different routes, influences the efficacy of T-cell-mediated therapy. ADAM10 cleaves CD8+ T-cell-targeting genes and impacts their expression and specificity. In addition, ADAM10 mediates the interactions of adhesion molecules with T cells and influences CD8+ T-cell activity and trafficking. Thus, understanding the role of ADAM10 in these events may lead to innovative strategies for advancing T-cell-mediated therapies.
T 细胞介导的治疗策略是癌症免疫疗法中最有效的效应因子。然而,这种疗法在实体瘤中的一个重要障碍是破坏了抗癌免疫反应、癌症免疫循环、T 细胞启动、贩运和 T 细胞细胞毒性能力。因此,需要加强抗癌免疫反应,以提高 T 细胞介导疗法的有效性。肿瘤相关蛋白酶ADAM10、内皮细胞(EC)和细胞毒性CD8+ T细胞通过粘附、迁移和趋化机制进行复杂的交流,以促进抗癌免疫反应。ADAM10 对这些相互作用的复杂机制的确切影响仍不清楚。本文广泛探讨了ADAM10如何通过不同途径影响T细胞介导疗法的疗效。ADAM10 可裂解 CD8+ T 细胞靶向基因并影响其表达和特异性。此外,ADAM10 还介导粘附分子与 T 细胞的相互作用,并影响 CD8+ T 细胞的活性和迁移。因此,了解 ADAM10 在这些事件中的作用可能会为推进 T 细胞介导的疗法带来创新策略。
{"title":"ADAM10 modulates the efficacy of T-cell-mediated therapy in solid tumors.","authors":"Ahmed Me Abdalla, Yu Miao, Ning Ming, Chenxi Ouyang","doi":"10.1111/imcb.12826","DOIUrl":"10.1111/imcb.12826","url":null,"abstract":"<p><p>T-cell-mediated therapeutic strategies are the most potent effectors of cancer immunotherapy. However, an essential barrier to this therapy in solid tumors is disrupting the anti-cancer immune response, cancer-immunity cycle, T-cell priming, trafficking and T-cell cytotoxic capacity. Thus, reinforcing the anti-cancer immune response is needed to improve the effectiveness of T-cell-mediated therapy. Tumor-associated protease ADAM10, endothelial cells (ECs) and cytotoxic CD8<sup>+</sup> T cells engage in complex communication via adhesion, transmigration and chemotactic mechanisms to facilitate an anti-cancer immune response. The precise impact of ADAM10 on the intricate mechanisms underlying these interactions remains unclear. This paper broadly explores how ADAM10, through different routes, influences the efficacy of T-cell-mediated therapy. ADAM10 cleaves CD8<sup>+</sup> T-cell-targeting genes and impacts their expression and specificity. In addition, ADAM10 mediates the interactions of adhesion molecules with T cells and influences CD8<sup>+</sup> T-cell activity and trafficking. Thus, understanding the role of ADAM10 in these events may lead to innovative strategies for advancing T-cell-mediated therapies.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454135","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}
Pub Date : 2024-11-01Epub Date: 2024-11-04DOI: 10.1111/imcb.12832
Jessica G Borger
In science and academia, success is often shaped by both knowledge and networking. Reflecting on nearly two decades in academic research, I recount my experience as a postdoctoral immunologist returning to Australia with limited local connections and support. Upon re-establishing myself in Australia, I initially faced barriers that restricted my visibility and collaborations. A turning point came when personal challenges motivated me to actively network, leading to valuable collaborations and career opportunities. By initiating conversations with academic leaders and peers, I expanded my network and established numerous leadership roles, even as a "junior" postdoc through founding a symposium, engaging with an immunology society, volunteering on various academic and advocacy committees, contributing to public outreach and nationally advocating for gender equity in science. These experiences reinforced that networking is about fostering meaningful relationships and creating opportunities to grow professionally. I provide advice on how to increase your networks by volunteering at work, when attending conferences, through contributing to societies and building a social media presence. My journey highlights the importance of being proactive in building networks, which can open doors, amplify one's voice, and drive career advancement in science and academia.
{"title":"The power of networking in science and academia.","authors":"Jessica G Borger","doi":"10.1111/imcb.12832","DOIUrl":"10.1111/imcb.12832","url":null,"abstract":"<p><p>In science and academia, success is often shaped by both knowledge and networking. Reflecting on nearly two decades in academic research, I recount my experience as a postdoctoral immunologist returning to Australia with limited local connections and support. Upon re-establishing myself in Australia, I initially faced barriers that restricted my visibility and collaborations. A turning point came when personal challenges motivated me to actively network, leading to valuable collaborations and career opportunities. By initiating conversations with academic leaders and peers, I expanded my network and established numerous leadership roles, even as a \"junior\" postdoc through founding a symposium, engaging with an immunology society, volunteering on various academic and advocacy committees, contributing to public outreach and nationally advocating for gender equity in science. These experiences reinforced that networking is about fostering meaningful relationships and creating opportunities to grow professionally. I provide advice on how to increase your networks by volunteering at work, when attending conferences, through contributing to societies and building a social media presence. My journey highlights the importance of being proactive in building networks, which can open doors, amplify one's voice, and drive career advancement in science and academia.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567006","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}
Shangwei Yang, Yanhe Zheng, Zhenjun Pu, Hongyu Nian, Junliang Li
Peritoneal adhesion (PA) refers to the abnormal adhesion of the peritoneum either with the peritoneum itself or with tissues and organs that is caused by abdominopelvic surgery, abdominal infection or peritoneal inflammation. PA is associated with various clinical complications, such as abdominal pain and distension, intestinal obstruction, gastrointestinal disorders and female infertility, and adversely affects the quality of life of patients. Macrophages are essential for PA formation and can undergo polarization into classically activated macrophages (M1) and alternatively activated macrophages (M2), which are influenced by the peritoneal microenvironment. By releasing proinflammatory cytokines and reactive oxygen species, M1 macrophages promote peritoneal inflammatory reactions and the resultant formation of adhesion. In contrast, M2 macrophages secrete anti-inflammatory cytokines and growth factors to inhibit PA formation and to promote repair and healing of peritoneal tissues, and thereby play a significant anti-inflammatory role. This review comprehensively explores the function and mechanism of macrophages and their subtypes in PA formation to gain insight into the prevention and treatment of PA based on the modulation of macrophages.
腹膜粘连(PA)是指腹盆腔手术、腹腔感染或腹膜炎症引起的腹膜与腹膜本身或与组织器官的异常粘连。PA 与多种临床并发症有关,如腹痛和腹胀、肠梗阻、胃肠功能紊乱和女性不孕,并对患者的生活质量产生不利影响。巨噬细胞对 PA 的形成至关重要,可极化为经典活化巨噬细胞(M1)和另类活化巨噬细胞(M2),后者受腹膜微环境的影响。M1 巨噬细胞通过释放促炎细胞因子和活性氧,促进腹膜炎症反应和粘连的形成。相反,M2 巨噬细胞分泌抗炎细胞因子和生长因子,抑制 PA 的形成,促进腹膜组织的修复和愈合,从而发挥重要的抗炎作用。本综述全面探讨了巨噬细胞及其亚型在 PA 形成过程中的功能和机制,从而深入了解基于巨噬细胞调节的 PA 预防和治疗方法。
{"title":"The multiple roles of macrophages in peritoneal adhesion.","authors":"Shangwei Yang, Yanhe Zheng, Zhenjun Pu, Hongyu Nian, Junliang Li","doi":"10.1111/imcb.12831","DOIUrl":"https://doi.org/10.1111/imcb.12831","url":null,"abstract":"<p><p>Peritoneal adhesion (PA) refers to the abnormal adhesion of the peritoneum either with the peritoneum itself or with tissues and organs that is caused by abdominopelvic surgery, abdominal infection or peritoneal inflammation. PA is associated with various clinical complications, such as abdominal pain and distension, intestinal obstruction, gastrointestinal disorders and female infertility, and adversely affects the quality of life of patients. Macrophages are essential for PA formation and can undergo polarization into classically activated macrophages (M1) and alternatively activated macrophages (M2), which are influenced by the peritoneal microenvironment. By releasing proinflammatory cytokines and reactive oxygen species, M1 macrophages promote peritoneal inflammatory reactions and the resultant formation of adhesion. In contrast, M2 macrophages secrete anti-inflammatory cytokines and growth factors to inhibit PA formation and to promote repair and healing of peritoneal tissues, and thereby play a significant anti-inflammatory role. This review comprehensively explores the function and mechanism of macrophages and their subtypes in PA formation to gain insight into the prevention and treatment of PA based on the modulation of macrophages.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542357","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}
Challenges don't last; embracing them is crucial to growth and success. Knowing and absorbing this is very important for students in any program and at any level in the academic world. I have my bachelor's and master's degrees from Ladoke Akintola University of Technology and University of Ibadan, Nigeria, respectively. Currently, I am a doctorate student at the Department of Immunology, University of Sao Paulo, Brazil. This article discusses my adaptation to a new environment, overcoming challenges, and the importance of support systems.
{"title":"Strive, Thrive & Survive: embracing challenges in pursuit of passion.","authors":"Abolaji Samson Olagunju","doi":"10.1111/imcb.12827","DOIUrl":"https://doi.org/10.1111/imcb.12827","url":null,"abstract":"<p><p>Challenges don't last; embracing them is crucial to growth and success. Knowing and absorbing this is very important for students in any program and at any level in the academic world. I have my bachelor's and master's degrees from Ladoke Akintola University of Technology and University of Ibadan, Nigeria, respectively. Currently, I am a doctorate student at the Department of Immunology, University of Sao Paulo, Brazil. This article discusses my adaptation to a new environment, overcoming challenges, and the importance of support systems.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491657","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}