Pub Date : 2022-01-01Epub Date: 2021-07-25DOI: 10.1080/08830185.2021.1955876
Hai-Cun Zhou, Xin-Yan Yan, Wen-Wen Yu, Xiao-Qin Liang, Xiao-Yan Du, Zhi-Chang Liu, Jian-Ping Long, Guang-Hui Zhao, Hong-Bin Liu
Metabolite lactic acid has always been regarded as a metabolic by-product rather than a bioactive molecule. Recently, this view has changed since it was discovered that lactic acid can be used as a signal molecule and has novel signal transduction functions both intracellular and extracellular, which can regulate key functions in the immune system. In recent years, more and more evidence has shown that lactic acid is closely related to the metabolism and polarization of macrophages. During inflammation, lactic acid is a regulator of macrophage metabolism, and it can prevent excessive inflammatory responses; In malignant tumors, lactic acid produced by tumor tissues promotes the polarization of tumor-associated macrophages, which in turn promotes tumor progression. In this review, we examined the relationship between lactic acid and macrophage metabolism. We further discussed how lactic acid plays a role in maintaining the homeostasis of macrophages, as well as the biology of macrophage polarization and the M1/M2 imbalance in human diseases. Potential methods to target lactic acid in the treatment of inflammation and cancer will also be discussed so as to provide new strategies for the treatment of diseases.
{"title":"Lactic acid in macrophage polarization: The significant role in inflammation and cancer.","authors":"Hai-Cun Zhou, Xin-Yan Yan, Wen-Wen Yu, Xiao-Qin Liang, Xiao-Yan Du, Zhi-Chang Liu, Jian-Ping Long, Guang-Hui Zhao, Hong-Bin Liu","doi":"10.1080/08830185.2021.1955876","DOIUrl":"https://doi.org/10.1080/08830185.2021.1955876","url":null,"abstract":"<p><p>Metabolite lactic acid has always been regarded as a metabolic by-product rather than a bioactive molecule. Recently, this view has changed since it was discovered that lactic acid can be used as a signal molecule and has novel signal transduction functions both intracellular and extracellular, which can regulate key functions in the immune system. In recent years, more and more evidence has shown that lactic acid is closely related to the metabolism and polarization of macrophages. During inflammation, lactic acid is a regulator of macrophage metabolism, and it can prevent excessive inflammatory responses; In malignant tumors, lactic acid produced by tumor tissues promotes the polarization of tumor-associated macrophages, which in turn promotes tumor progression. In this review, we examined the relationship between lactic acid and macrophage metabolism. We further discussed how lactic acid plays a role in maintaining the homeostasis of macrophages, as well as the biology of macrophage polarization and the M1/M2 imbalance in human diseases. Potential methods to target lactic acid in the treatment of inflammation and cancer will also be discussed so as to provide new strategies for the treatment of diseases.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/08830185.2021.1955876","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39219765","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 : 2022-01-01Epub Date: 2021-01-07DOI: 10.1080/08830185.2020.1861265
Tue Gia Nguyen
Immunoglobulin D (IgD) is an enigmatic antibody and the least appreciated member of the immunoglobulin (Ig) family. Since its discovery over half a century ago, the essence of its function in the immune system has been somewhat enigmatic and less well-defined than other antibody classes. Membrane-bound IgD (mIgD) is mostly recognized as B-cell receptor (BCR) while secreted IgD (sIgD) has been recently implicated in 'arming' basophils and mast cells in mucosal innate immunity. Activations of immune responses via mIgD-BCR or sIgD by specific antigens or anti-IgD antibody thereby produce a broad and complex mix of cellular, antibody and cytokine responses from both the innate and adaptive immune systems. Such broadly activated immune responses via IgD were initially deemed to potentiate and exacerbate the onset of autoimmune and allergic conditions. Paradoxically, treatments with anti-IgD antibody suppressed and ameliorated autoimmune conditions and allergic inflammations in mouse models without compromising the host's general immune defence, demonstrating a unique and novel therapeutic application for anti-IgD antibody treatment. Herein, this review endeavored to collate and summarize the evidence of the unique characteristics and features of activated immune responses via mIgD-BCR and sIgD that revealed an unappreciated immune-regulatory function of IgD in the immune system via an amplifying loop of anti-inflammatory Th2 and tolerogenic responses, and highlighted a novel therapeutic paradigm in harnessing these immune responses to treat human autoimmune and allergic conditions.
{"title":"The therapeutic implications of activated immune responses via the enigmatic immunoglobulin D.","authors":"Tue Gia Nguyen","doi":"10.1080/08830185.2020.1861265","DOIUrl":"https://doi.org/10.1080/08830185.2020.1861265","url":null,"abstract":"<p><p>Immunoglobulin D (IgD) is an enigmatic antibody and the least appreciated member of the immunoglobulin (Ig) family. Since its discovery over half a century ago, the essence of its function in the immune system has been somewhat enigmatic and less well-defined than other antibody classes. Membrane-bound IgD (mIgD) is mostly recognized as B-cell receptor (BCR) while secreted IgD (sIgD) has been recently implicated in 'arming' basophils and mast cells in mucosal innate immunity. Activations of immune responses via mIgD-BCR or sIgD by specific antigens or anti-IgD antibody thereby produce a broad and complex mix of cellular, antibody and cytokine responses from both the innate and adaptive immune systems. Such broadly activated immune responses via IgD were initially deemed to potentiate and exacerbate the onset of autoimmune and allergic conditions. Paradoxically, treatments with anti-IgD antibody suppressed and ameliorated autoimmune conditions and allergic inflammations in mouse models without compromising the host's general immune defence, demonstrating a unique and novel therapeutic application for anti-IgD antibody treatment. Herein, this review endeavored to collate and summarize the evidence of the unique characteristics and features of activated immune responses via mIgD-BCR and sIgD that revealed an unappreciated immune-regulatory function of IgD in the immune system via an amplifying loop of anti-inflammatory Th2 and tolerogenic responses, and highlighted a novel therapeutic paradigm in harnessing these immune responses to treat human autoimmune and allergic conditions.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/08830185.2020.1861265","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38793147","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 : 2022-01-01Epub Date: 2021-05-12DOI: 10.1080/08830185.2021.1925267
Asim Biswas, Rahul Shubhra Mandal, Suparna Chakraborty, George Maiti
The impact of SARS-CoV-2 and COVID-19 disease susceptibility varies depending on the age and health status of an individual. Currently, there are more than 140 COVID-19 vaccines under development. However, the challenge will be to induce an effective immune response in the elderly population. Analysis of B cell epitopes indicates the minor role of the stalk domain of spike protein in viral neutralization due to low surface accessibility. Nevertheless, the accumulation of mutations in the receptor-binding domain (RBD) might reduce the vaccine efficacy in all age groups. We also propose the concept of chimeric vaccines based on the co-expression of SARS-CoV-2 spike and influenza hemagglutinin (HA) and matrix protein 1 (M1) proteins to generate chimeric virus-like particles (VLP). This review discusses the possible approaches by which influenza-specific memory repertoire developed during the lifetime of the elderly populations can converge to mount an effective immune response against the SARS-CoV-2 spike protein with the possibilities of designing single vaccines for COVID-19 and influenza. HighlightsImmunosenescence aggravates COVID-19 symptoms in elderly individuals.Low immunogenicity of SARS-CoV-2 vaccines in elderly population.Tapping the memory T and B cell repertoire in elderly can enhance vaccine efficiency.Chimeric vaccines can mount effective immune response against COVID-19 in elderly.Chimeric vaccines co-express SARS-CoV-2 spike and influenza HA and M1 proteins.
SARS-CoV-2 和 COVID-19 疾病易感性的影响因个人的年龄和健康状况而异。目前,有 140 多种 COVID-19 疫苗正在开发中。然而,如何在老年人群中诱导有效的免疫反应将是一项挑战。对 B 细胞表位的分析表明,尖峰蛋白的柄结构域由于表面可及性低,在病毒中和中发挥的作用很小。然而,受体结合域(RBD)突变的积累可能会降低疫苗在所有年龄组中的效力。我们还提出了嵌合疫苗的概念,它基于 SARS-CoV-2 穗状病毒与流感血凝素(HA)和基质蛋白 1(M1)蛋白的共同表达,从而产生嵌合病毒样颗粒(VLP)。本综述讨论了老年人群在有生之年形成的流感特异性记忆库汇聚到一起对 SARS-CoV-2 穗状病毒蛋白产生有效免疫反应的可能方法,以及设计 COVID-19 和流感单一疫苗的可能性。亮点免疫衰老会加重老年人的 COVID-19 症状.SARS-CoV-2 疫苗在老年人群中的免疫原性较低.利用老年人的记忆性 T 细胞和 B 细胞群可提高疫苗的效率.嵌合疫苗可使老年人对 COVID-19 产生有效的免疫反应.嵌合疫苗可共同表达 SARS-CoV-2 棘蛋白和流感 HA 及 M1 蛋白.SARS-CoV-2疫苗在老年人群中的免疫原性较低.嵌合疫苗可使老年人对 COVID-19 产生有效的免疫反应.嵌合疫苗可共同表达 SARS-CoV-2 棘蛋白和流感 HA 及 M1 蛋白.
{"title":"Tapping the immunological imprints to design chimeric SARS-CoV-2 vaccine for elderly population.","authors":"Asim Biswas, Rahul Shubhra Mandal, Suparna Chakraborty, George Maiti","doi":"10.1080/08830185.2021.1925267","DOIUrl":"10.1080/08830185.2021.1925267","url":null,"abstract":"<p><p>The impact of SARS-CoV-2 and COVID-19 disease susceptibility varies depending on the age and health status of an individual. Currently, there are more than 140 COVID-19 vaccines under development. However, the challenge will be to induce an effective immune response in the elderly population. Analysis of B cell epitopes indicates the minor role of the stalk domain of spike protein in viral neutralization due to low surface accessibility. Nevertheless, the accumulation of mutations in the receptor-binding domain (RBD) might reduce the vaccine efficacy in all age groups. We also propose the concept of chimeric vaccines based on the co-expression of SARS-CoV-2 spike and influenza hemagglutinin (HA) and matrix protein 1 (M1) proteins to generate chimeric virus-like particles (VLP). This review discusses the possible approaches by which influenza-specific memory repertoire developed during the lifetime of the elderly populations can converge to mount an effective immune response against the SARS-CoV-2 spike protein with the possibilities of designing single vaccines for COVID-19 and influenza. HighlightsImmunosenescence aggravates COVID-19 symptoms in elderly individuals.Low immunogenicity of SARS-CoV-2 vaccines in elderly population.Tapping the memory T and B cell repertoire in elderly can enhance vaccine efficiency.Chimeric vaccines can mount effective immune response against COVID-19 in elderly.Chimeric vaccines co-express SARS-CoV-2 spike and influenza HA and M1 proteins.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127164/pdf/IIRI_0_1925267.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38972347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2021-02-12DOI: 10.1080/08830185.2021.1884247
Yan-Cun Liu, Song-Tao Shou, Yan-Fen Chai
Sepsis is a life-threatening syndrome with a high incidence and a weighty economic burden. The cytokines storm in the early stage and the state of immunosuppression in the late stage contribute to the mortality of sepsis. Immune checkpoints expressed on lymphocytes and APCs, including CD28, CTLA-4, CD80, CD86, PD-1 and PD-L1, CD40 and CD40L, OX40 and OX40L, 4-1BB and 4-1BBL, BTLA, TIM family, play significant roles in the pathogenesis of sepsis through regulating the immune disorder. The specific therapies targeting immune checkpoints exhibit great potentials in the animal and preclinical studies, and further clinical trials are planning to implement. Here, we review the current literature on the roles played by immune checkpoints in the pathogenesis and treatment of sepsis. We hope to provide further insights into this novel immunomodulatory strategy.
{"title":"Immune checkpoints in sepsis: New hopes and challenges.","authors":"Yan-Cun Liu, Song-Tao Shou, Yan-Fen Chai","doi":"10.1080/08830185.2021.1884247","DOIUrl":"https://doi.org/10.1080/08830185.2021.1884247","url":null,"abstract":"<p><p>Sepsis is a life-threatening syndrome with a high incidence and a weighty economic burden. The cytokines storm in the early stage and the state of immunosuppression in the late stage contribute to the mortality of sepsis. Immune checkpoints expressed on lymphocytes and APCs, including CD28, CTLA-4, CD80, CD86, PD-1 and PD-L1, CD40 and CD40L, OX40 and OX40L, 4-1BB and 4-1BBL, BTLA, TIM family, play significant roles in the pathogenesis of sepsis through regulating the immune disorder. The specific therapies targeting immune checkpoints exhibit great potentials in the animal and preclinical studies, and further clinical trials are planning to implement. Here, we review the current literature on the roles played by immune checkpoints in the pathogenesis and treatment of sepsis. We hope to provide further insights into this novel immunomodulatory strategy.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/08830185.2021.1884247","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25363769","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 : 2022-01-01Epub Date: 2021-10-05DOI: 10.1080/08830185.2021.1984449
Vahid Mansouri, Niloufar Yazdanpanah, Nima Rezaei
Chimeric antigen receptor (CAR) T cells are the pioneers of cancer immunotherapy, which to this date have several FDA-approved products. They have been substantially improved since their first introduction in 1993 and have shown promising results regardless of their inevitable side effects. Cytokine release syndrome (CRS), the most common toxicity after CAR T cell treatment, is affiliated to a systemic inflammation through surge of cytokines, mainly IL-6, IL-1, and INF-γ. Furthermore, difference between histocompatibility antigens activates the graft versus host disease (GvHD) effect of the allogenic CAR T cells against the host cells. Immunological reactions induced by CAR T cells in the form of CRS or GvHD is necessary for fostering good responses, while excess reactions can potentially threaten patient life. In this review, we first describe the history, applications, and structure of CAR T cells, followed by a comprehensive review of CRS regarding its definition, management, and immunological aspects. Finally, we discuss about the clinical aspects of CRS and GvHD after CAR T cell therapy and how to harness anti-tumoral effects, while mitigating the adverse effects.
{"title":"The immunologic aspects of cytokine release syndrome and graft versus host disease following CAR T cell therapy.","authors":"Vahid Mansouri, Niloufar Yazdanpanah, Nima Rezaei","doi":"10.1080/08830185.2021.1984449","DOIUrl":"https://doi.org/10.1080/08830185.2021.1984449","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T cells are the pioneers of cancer immunotherapy, which to this date have several FDA-approved products. They have been substantially improved since their first introduction in 1993 and have shown promising results regardless of their inevitable side effects. Cytokine release syndrome (CRS), the most common toxicity after CAR T cell treatment, is affiliated to a systemic inflammation through surge of cytokines, mainly IL-6, IL-1, and INF-γ. Furthermore, difference between histocompatibility antigens activates the graft versus host disease (GvHD) effect of the allogenic CAR T cells against the host cells. Immunological reactions induced by CAR T cells in the form of CRS or GvHD is necessary for fostering good responses, while excess reactions can potentially threaten patient life. In this review, we first describe the history, applications, and structure of CAR T cells, followed by a comprehensive review of CRS regarding its definition, management, and immunological aspects. Finally, we discuss about the clinical aspects of CRS and GvHD after CAR T cell therapy and how to harness anti-tumoral effects, while mitigating the adverse effects.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39484927","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 : 2022-01-01Epub Date: 2021-05-26DOI: 10.1080/08830185.2021.1921174
Abraham U Morales-Primo, Ingeborg Becker, Jaime Zamora-Chimal
Neutrophil extracellular traps (NETs) are a defense mechanism against pathogens. They are composed of DNA and various proteins and have the ability to hinder microbial spreading and survival. However, NETs are not only related to infections but also participate in sterile inflammatory events. In addition to DNA, NETs contain histones, serine proteases, cytoskeletal proteins and antimicrobial peptides, all of which have immunomodulatory properties that can augment or decrease the inflammatory response. Extracellular localization of these molecules alerts the immune system of cellular damage, which is triggered by recognition of damage-associated molecular patterns (DAMPs) through specific pattern recognition receptors. However, not all of these molecules are DAMPs and may have other immunophysiological properties in the extracellular space. The release of NETs can lead to production of pro-inflammatory cytokines (due to TLR2/4/9 and inflammasome activation), the destruction of the extracellular matrix, activation of serine proteases and of matrix metallopeptidases (MMPs), modulation of cellular proliferation, induction of cellular migration and adhesion, promotion of thrombogenesis and angiogenesis and disruption of epithelial and endothelial permeability. Understanding the dynamics of NET-associated molecules, either individually or synergically, will help to unravel their role in inflammatory events and open novel perspectives for potential therapeutic targets. We here review molecules contained within NETS and their immunophysiological roles.
{"title":"Neutrophil extracellular trap-associated molecules: a review on their immunophysiological and inflammatory roles.","authors":"Abraham U Morales-Primo, Ingeborg Becker, Jaime Zamora-Chimal","doi":"10.1080/08830185.2021.1921174","DOIUrl":"https://doi.org/10.1080/08830185.2021.1921174","url":null,"abstract":"<p><p>Neutrophil extracellular traps (NETs) are a defense mechanism against pathogens. They are composed of DNA and various proteins and have the ability to hinder microbial spreading and survival. However, NETs are not only related to infections but also participate in sterile inflammatory events. In addition to DNA, NETs contain histones, serine proteases, cytoskeletal proteins and antimicrobial peptides, all of which have immunomodulatory properties that can augment or decrease the inflammatory response. Extracellular localization of these molecules alerts the immune system of cellular damage, which is triggered by recognition of damage-associated molecular patterns (DAMPs) through specific pattern recognition receptors. However, not all of these molecules are DAMPs and may have other immunophysiological properties in the extracellular space. The release of NETs can lead to production of pro-inflammatory cytokines (due to TLR2/4/9 and inflammasome activation), the destruction of the extracellular matrix, activation of serine proteases and of matrix metallopeptidases (MMPs), modulation of cellular proliferation, induction of cellular migration and adhesion, promotion of thrombogenesis and angiogenesis and disruption of epithelial and endothelial permeability. Understanding the dynamics of NET-associated molecules, either individually or synergically, will help to unravel their role in inflammatory events and open novel perspectives for potential therapeutic targets. We here review molecules contained within NETS and their immunophysiological roles.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/08830185.2021.1921174","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39020140","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}
Abstract Behçet's disease (BD) is a systemic and inflammatory disease, characterized mainly by recurrent oral and genital ulcers, eye involvement, and skin lesions. Although the exact etiopathogenesis of BD remains unrevealed, a bulk of studies have implicated the genetic contributing factors as critical players in disease predisposition. In countries along the Silk Road, human leukocyte antigen (HLA)-B51 has been reported as the strongest genetically associated factor for BD. Genome-wide association studies, local genetic polymorphism studies, and meta-analysis of combined data from Turkish, Iranian, and Japanese populations have also identified new genetic associations with BD. Among these, other HLA alleles such as HLA-B*15, HLA-B*27, HLA-B*57, and HLA-A*26 have been found as independent risk factors for BD, whereas HLA-B*49 and HLA-A*03 are independent protective alleles for BD. Moreover, other genes have also reached the genome-wide significance level of association with BD susceptibility, including IL10, IL23R-IL12RB2, IL12A, CCR1-CCR3, STAT4, TNFAIP3, ERAP1, KLRC4, and FUT2. Also, several rare nonsynonymous variants in TLR4, IL23R, NOD2, and MEFV genes have been reported to be involved in BD pathogenesis. According to genetic determinants in the loci outside the MHC region that are contributed to the host defense, immunity, and inflammation pathways, it is suggested that immune responses to the pathogen as an important environmental factor and mucosal immunity contribute to BD susceptibility.
behet病(BD)是一种全身性炎症性疾病,主要表现为复发性口腔和生殖器溃疡、眼部受累和皮肤病变。虽然双相障碍的确切发病机制尚不清楚,但大量研究表明遗传因素是疾病易感性的关键因素。在丝绸之路沿线国家,人类白细胞抗原(HLA)-B51被报道为双相障碍最强的遗传相关因素。全基因组关联研究、当地遗传多态性研究以及土耳其、伊朗和日本人群的综合数据荟萃分析也发现了与双相障碍的新的遗传关联。其中,HLA- b *15、HLA- b *27、HLA- b *57和HLA- a *26等HLA等位基因也被发现是双相障碍的独立危险因素。而HLA-B*49和HLA-A*03是独立的BD保护性等位基因。此外,其他与BD易感性相关的基因也达到了全基因组显著水平,包括IL10、IL23R-IL12RB2、IL12A、CCR1-CCR3、STAT4、TNFAIP3、ERAP1、KLRC4和FUT2。此外,一些罕见的TLR4、IL23R、NOD2和MEFV基因的非同义变异也被报道参与了双相障碍的发病机制。根据MHC区域外基因座中参与宿主防御、免疫和炎症途径的遗传决定因素,提示对病原体的免疫反应是一个重要的环境因素,粘膜免疫是BD易感性的因素。
{"title":"A comprehensive overview on the genetics of Behçet's disease.","authors":"Mahdi Mahmoudi, Saeed Aslani, Akira Meguro, Maryam Akhtari, Yousef Fatahi, Nobuhisa Mizuki, Farhad Shahram","doi":"10.1080/08830185.2020.1851372","DOIUrl":"https://doi.org/10.1080/08830185.2020.1851372","url":null,"abstract":"Abstract Behçet's disease (BD) is a systemic and inflammatory disease, characterized mainly by recurrent oral and genital ulcers, eye involvement, and skin lesions. Although the exact etiopathogenesis of BD remains unrevealed, a bulk of studies have implicated the genetic contributing factors as critical players in disease predisposition. In countries along the Silk Road, human leukocyte antigen (HLA)-B51 has been reported as the strongest genetically associated factor for BD. Genome-wide association studies, local genetic polymorphism studies, and meta-analysis of combined data from Turkish, Iranian, and Japanese populations have also identified new genetic associations with BD. Among these, other HLA alleles such as HLA-B*15, HLA-B*27, HLA-B*57, and HLA-A*26 have been found as independent risk factors for BD, whereas HLA-B*49 and HLA-A*03 are independent protective alleles for BD. Moreover, other genes have also reached the genome-wide significance level of association with BD susceptibility, including IL10, IL23R-IL12RB2, IL12A, CCR1-CCR3, STAT4, TNFAIP3, ERAP1, KLRC4, and FUT2. Also, several rare nonsynonymous variants in TLR4, IL23R, NOD2, and MEFV genes have been reported to be involved in BD pathogenesis. According to genetic determinants in the loci outside the MHC region that are contributed to the host defense, immunity, and inflammation pathways, it is suggested that immune responses to the pathogen as an important environmental factor and mucosal immunity contribute to BD susceptibility.","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/08830185.2020.1851372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38657731","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 : 2022-01-01DOI: 10.1080/08830185.2022.2067154
Hannah W Song, Robert P Somerville, David F Stroncek, Steven L Highfill
Engineered T cell therapies such as CAR-T cells and TCR-T cells have generated impressive patient responses in previously incurable diseases. In the past few years there have been a number of technical innovations that enable robust clinical manufacturing in functionally closed and often automated systems. Here we describe the latest technology used to manufacture CAR- and TCR-engineered T cells in the clinic, including cell purification, transduction/transfection, expansion and harvest. To help compare the different systems available, we present three case studies of engineered T cells manufactured for phase I clinical trials at the NIH Clinical Center (CD30 CAR-T cells for lymphoma, CD19/CD22 bispecific CAR-T cells for B cell malignancies, and E7 TCR T cells for human papilloma virus-associated cancers). Continued improvement in cell manufacturing technology will help enable world-wide implementation of engineered T cell therapies.
{"title":"Scaling up and scaling out: Advances and challenges in manufacturing engineered T cell therapies.","authors":"Hannah W Song, Robert P Somerville, David F Stroncek, Steven L Highfill","doi":"10.1080/08830185.2022.2067154","DOIUrl":"https://doi.org/10.1080/08830185.2022.2067154","url":null,"abstract":"<p><p>Engineered T cell therapies such as CAR-T cells and TCR-T cells have generated impressive patient responses in previously incurable diseases. In the past few years there have been a number of technical innovations that enable robust clinical manufacturing in functionally closed and often automated systems. Here we describe the latest technology used to manufacture CAR- and TCR-engineered T cells in the clinic, including cell purification, transduction/transfection, expansion and harvest. To help compare the different systems available, we present three case studies of engineered T cells manufactured for phase I clinical trials at the NIH Clinical Center (CD30 CAR-T cells for lymphoma, CD19/CD22 bispecific CAR-T cells for B cell malignancies, and E7 TCR T cells for human papilloma virus-associated cancers). Continued improvement in cell manufacturing technology will help enable world-wide implementation of engineered T cell therapies.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9815724/pdf/nihms-1848290.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9730554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2021-09-16DOI: 10.1080/08830185.2021.1967949
Afsar R Naqvi, Joel Schwartz, Daniela Atili Brandini, Samantha Schaller, Heba Hussein, Araceli Valverde, Raza Ali Naqvi, Deepak Shukla
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a recently identified virus responsible for life-threatening coronavirus disease 19 (COVID-19). The SARS-CoV-2 infected subjects can be asymptomatic or symptomatic; the later may present a wide spectrum of clinical manifestations. However, the impact of SARS-CoV-2 on oral diseases remain poorly studied. Detection of SARS-CoV-2 in saliva indicates existence of virus in the oral cavity. Recent studies demonstrating the expression of ACE-2, a SARS-CoV-2 entry receptor, in oral tissues further strengthens this observation. Cytokine storm in severe COVID-19 patients and copious secretion of pro-inflammatory cytokines (IL-6, IL-1β and TNF-α) in multiple symptomatic oral pathologies including periodontitis and periapical periodontitis suggests that inflammatory microenvironment is a hallmark of both COVID-19 and oral diseases. Hyperinflammation may provide conducive microenvironment for the growth of local oral pathogens or opportunistic microbes and exert detrimental impact on the oral tissue integrity. Multiple case reports have indicated uncharacterized oral lesions, symptomatic irreversible pulpitis, higher plaque index, necrotizing/desquamative gingivitis in COVID-19 patients suggesting that SARS-CoV-2 may worsen the manifestations of oral infections. However, the underlying factors and pathways remain elusive. Here we summarize current literature and suggest mechanisms for viral pathogenesis of oral dental pathology derived from oral microbiome and oral mucosa-dental tissue interactions. Longitudinal studies will reveal how the virus impairs disease progression and resolution post-therapy. Some relationships we suggest provide the basis for novel monitoring and treatment of oral viral disease in the era of SARS-CoV-2 pandemic, promoting evidence-based dentistry guidelines to diagnose virus-infected patients to improve oral health.
{"title":"COVID-19 and oral diseases: Assessing manifestations of a new pathogen in oral infections.","authors":"Afsar R Naqvi, Joel Schwartz, Daniela Atili Brandini, Samantha Schaller, Heba Hussein, Araceli Valverde, Raza Ali Naqvi, Deepak Shukla","doi":"10.1080/08830185.2021.1967949","DOIUrl":"https://doi.org/10.1080/08830185.2021.1967949","url":null,"abstract":"<p><p>Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a recently identified virus responsible for life-threatening coronavirus disease 19 (COVID-19). The SARS-CoV-2 infected subjects can be asymptomatic or symptomatic; the later may present a wide spectrum of clinical manifestations. However, the impact of SARS-CoV-2 on oral diseases remain poorly studied. Detection of SARS-CoV-2 in saliva indicates existence of virus in the oral cavity. Recent studies demonstrating the expression of ACE-2, a SARS-CoV-2 entry receptor, in oral tissues further strengthens this observation. Cytokine storm in severe COVID-19 patients and copious secretion of pro-inflammatory cytokines (IL-6, IL-1β and TNF-α) in multiple symptomatic oral pathologies including periodontitis and periapical periodontitis suggests that inflammatory microenvironment is a hallmark of both COVID-19 and oral diseases. Hyperinflammation may provide conducive microenvironment for the growth of local oral pathogens or opportunistic microbes and exert detrimental impact on the oral tissue integrity. Multiple case reports have indicated uncharacterized oral lesions, symptomatic irreversible pulpitis, higher plaque index, necrotizing/desquamative gingivitis in COVID-19 patients suggesting that SARS-CoV-2 may worsen the manifestations of oral infections. However, the underlying factors and pathways remain elusive. Here we summarize current literature and suggest mechanisms for viral pathogenesis of oral dental pathology derived from oral microbiome and oral mucosa-dental tissue interactions. Longitudinal studies will reveal how the virus impairs disease progression and resolution post-therapy. Some relationships we suggest provide the basis for novel monitoring and treatment of oral viral disease in the era of SARS-CoV-2 pandemic, promoting evidence-based dentistry guidelines to diagnose virus-infected patients to improve oral health.</p>","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39419073","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 : 2022-01-01Epub Date: 2021-09-06DOI: 10.1080/08830185.2021.1974856
Ying Luo, Lu Li, Xu Chen, Huiqing Gou, Ke Yan, Yan Xu
Abstract Lactate used to be considered as a waste product of glucose metabolism. However, accumulating evidence has revealed its crucial role in regulating various biological and pathological processes. Hypoxia, inflammation, viral infection, and tumor promote the production of lactate. Then lactate activates G protein-coupled receptor 81 (GPR81) or shuttles across membranes by monocarboxylate-transporters (MCTs) to execute its intricate effects. Many studies highlighted the function of lactate in regulating dendritic cells, monocytes, natural killer cells, mast cells, T cells, tumor cells, fibroblasts, macrophages polarization, and the differentiation of Th1, Th17, MDSCs, Tregs; all of which play a role in maintaining the immune homeostasis of the host when challenged with the noxious stimuli. In this review, we summarized the influence of lactate in diverse tissue-specific cells, and discuss their effects on viral infection, acute inflammation, chronic inflammation, sepsis, and tumor immunosuppression. The goal of this review is to expose that lactate has a double-edged effect on host immunity and accompanying inflammatory reactions, which could be a potentially effective target for treating the tumor and multiple infectious diseases. GRAPHICAL ABSTRACT
{"title":"Effects of lactate in immunosuppression and inflammation: Progress and prospects.","authors":"Ying Luo, Lu Li, Xu Chen, Huiqing Gou, Ke Yan, Yan Xu","doi":"10.1080/08830185.2021.1974856","DOIUrl":"https://doi.org/10.1080/08830185.2021.1974856","url":null,"abstract":"Abstract Lactate used to be considered as a waste product of glucose metabolism. However, accumulating evidence has revealed its crucial role in regulating various biological and pathological processes. Hypoxia, inflammation, viral infection, and tumor promote the production of lactate. Then lactate activates G protein-coupled receptor 81 (GPR81) or shuttles across membranes by monocarboxylate-transporters (MCTs) to execute its intricate effects. Many studies highlighted the function of lactate in regulating dendritic cells, monocytes, natural killer cells, mast cells, T cells, tumor cells, fibroblasts, macrophages polarization, and the differentiation of Th1, Th17, MDSCs, Tregs; all of which play a role in maintaining the immune homeostasis of the host when challenged with the noxious stimuli. In this review, we summarized the influence of lactate in diverse tissue-specific cells, and discuss their effects on viral infection, acute inflammation, chronic inflammation, sepsis, and tumor immunosuppression. The goal of this review is to expose that lactate has a double-edged effect on host immunity and accompanying inflammatory reactions, which could be a potentially effective target for treating the tumor and multiple infectious diseases. GRAPHICAL ABSTRACT","PeriodicalId":14333,"journal":{"name":"International Reviews of Immunology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39388163","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}