{"title":"Histone deacetylases as targets in autoimmune and autoinflammatory diseases.","authors":"Patricia Hamminger, Ramona Rica, Wilfried Ellmeier","doi":"10.1016/bs.ai.2020.06.001","DOIUrl":"https://doi.org/10.1016/bs.ai.2020.06.001","url":null,"abstract":"<p><p>Reversible lysine acetylation of histones is a key epigenetic regulatory process controlling gene expression. Reversible histone acetylation is mediated by two opposing enzyme families: histone acetyltransferases (HATs) and histone deacetylases (HDACs). Moreover, many non-histone targets of HATs and HDACs are known, suggesting a crucial role for lysine acetylation as a posttranslational modification on the cellular proteome and protein function far beyond chromatin-mediated gene regulation. The HDAC family consists of 18 members and pan-HDAC inhibitors (HDACi) are clinically used for the treatment of certain types of cancer. HDACi or individual HDAC member-deficient (cell lineage-specific) mice have also been tested in a large number of preclinical mouse models for several autoimmune and autoinflammatory diseases and in most cases HDACi treatment results in an attenuation of clinical disease severity. A reduction of disease severity has also been observed in mice lacking certain HDAC members. This indicates a high therapeutic potential of isoform-selective HDACi for immune-mediated diseases. Isoform-selective HDACi and thus targeted inactivation of HDAC isoforms might also overcome the adverse effects of current clinically approved pan-HDACi. This review provides a brief overview about the fundamental function of HDACs as epigenetic regulators, highlights the roles of HDACs beyond chromatin-mediated control of gene expression and summarizes the studies showing the impact of HDAC inhibitors and genetic deficiencies of HDAC members for the outcome of autoimmune and autoinflammatory diseases with a focus on rheumatoid arthritis, inflammatory bowel disease and experimental autoimmune encephalomyelitis (EAE) as an animal model of multiple sclerosis.</p>","PeriodicalId":50862,"journal":{"name":"Advances in Immunology","volume":"147 ","pages":"1-59"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.ai.2020.06.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9400607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advances in ImmunologyPub Date : 2020-01-01Epub Date: 2020-02-27DOI: 10.1016/bs.ai.2020.01.002
Wolfgang Schuh, Dirk Mielenz, Hans-Martin Jäck
{"title":"Unraveling the mysteries of plasma cells.","authors":"Wolfgang Schuh, Dirk Mielenz, Hans-Martin Jäck","doi":"10.1016/bs.ai.2020.01.002","DOIUrl":"https://doi.org/10.1016/bs.ai.2020.01.002","url":null,"abstract":"<p><p>Antibody-secreting plasma cells are the central pillars of humoral immunity. They are generated in a fundamental cellular restructuring process from naive B cells upon contact with antigen. This outstanding process is guided and controlled by a complex transcriptional network accompanied by a fascinating morphological metamorphosis, governed by the combined action of Blimp-1, Xbp-1 and IRF-4. The survival of plasma cells requires the intimate interaction with a specific microenvironment, consisting of stromal cells and cells of hematopoietic origin. Cell-cell contacts, cytokines and availability of metabolites such as glucose and amino acids modulate the survival abilities of plasma cells in their niches. Moreover, plasma cells have been shown to regulate immune responses by releasing cytokines. Furthermore, plasma cells are central players in autoimmune diseases and malignant transformation of plasma cells can result in the generation of multiple myeloma. Hence, the development of sophisticated strategies to deplete autoreactive plasma cells and myeloma cells represents a challenge for current and future research.</p>","PeriodicalId":50862,"journal":{"name":"Advances in Immunology","volume":"146 ","pages":"57-107"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.ai.2020.01.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37866017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Copyright","authors":"","doi":"10.1016/s0065-2776(20)30020-1","DOIUrl":"https://doi.org/10.1016/s0065-2776(20)30020-1","url":null,"abstract":"","PeriodicalId":50862,"journal":{"name":"Advances in Immunology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0065-2776(20)30020-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"55885671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advances in ImmunologyPub Date : 2020-01-01Epub Date: 2020-11-05DOI: 10.1016/bs.ai.2020.10.003
Yasmeen S El Ansari, Cynthia Kanagaratham, Owen L Lewis, Hans C Oettgen
{"title":"IgE and mast cells: The endogenous adjuvant.","authors":"Yasmeen S El Ansari, Cynthia Kanagaratham, Owen L Lewis, Hans C Oettgen","doi":"10.1016/bs.ai.2020.10.003","DOIUrl":"https://doi.org/10.1016/bs.ai.2020.10.003","url":null,"abstract":"<p><p>Mast cells and IgE are most familiar as the effectors of type I hypersensitivity reactions including anaphylaxis. It is becoming clear however that this pair has important immunomodulatory effects on innate and adaptive cells of the immune system. In this purview, they act as endogenous adjuvants to ignite evolving immune responses, promote the transition of allergic disease into chronic illness and disrupt the development of active mechanisms of tolerance to ingested foods. Suppression of IgE-mediated mast cell activation can be exerted by molecules targeting IgE, FcɛRI or signaling kinases including Syk, or by IgG antibodies acting via inhibitory Fcγ receptors. In 2015 we reviewed the evidence for the adjuvant functions of mast cells. This update includes the original text, incorporates some important developments in the field over the past five years and discusses how interventions targeting these pathways might have promise in the development of strategies to treat allergic disease.</p>","PeriodicalId":50862,"journal":{"name":"Advances in Immunology","volume":" ","pages":"93-153"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.ai.2020.10.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38689931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advances in ImmunologyPub Date : 2020-01-01Epub Date: 2019-12-09DOI: 10.1016/bs.ai.2019.11.004
Yi Zheng, Chengjiang Gao
{"title":"Fine-tuning of antiviral innate immunity by ubiquitination.","authors":"Yi Zheng, Chengjiang Gao","doi":"10.1016/bs.ai.2019.11.004","DOIUrl":"https://doi.org/10.1016/bs.ai.2019.11.004","url":null,"abstract":"<p><p>The innate immune system represents the first defense line of the host following viral infection. The infection triggers the recognition of pathogen-associated molecular patterns (PAMPs) from the viruses by pattern recognition receptors (PRRs) of the host cell. The interaction between viral PAMPs and PRRs evokes a sophisticated signal transduction system and eventually promotes the expression of type I interferons (IFNs) and proinflammatory cytokines. Ubiquitination plays an indispensable role in fine-tuning almost every single step of this signaling cascade given on its versatile functions. Ubiquitin ligases and deubiquitinases (DUBs), which cooperatively and accurately regulate the dynamic and reversible ubiquitination process, are the master regulators of antiviral signaling. In this review, we concentrate on summarizing the ubiquitin ligases and DUBs that modulate the central signaling molecules in antiviral innate immunity. Especially, we emphasize the ones that were identified by the immunologists from China.</p>","PeriodicalId":50862,"journal":{"name":"Advances in Immunology","volume":"145 ","pages":"95-128"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.ai.2019.11.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37661842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Contributors","authors":"","doi":"10.1016/s0065-2776(20)30048-1","DOIUrl":"https://doi.org/10.1016/s0065-2776(20)30048-1","url":null,"abstract":"","PeriodicalId":50862,"journal":{"name":"Advances in Immunology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0065-2776(20)30048-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"55885729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advances in ImmunologyPub Date : 2020-01-01Epub Date: 2020-02-26DOI: 10.1016/bs.ai.2020.01.001
Barbara L Kee, Rosmary E Morman, Mengxi Sun
{"title":"Transcriptional regulation of natural killer cell development and maturation.","authors":"Barbara L Kee, Rosmary E Morman, Mengxi Sun","doi":"10.1016/bs.ai.2020.01.001","DOIUrl":"https://doi.org/10.1016/bs.ai.2020.01.001","url":null,"abstract":"<p><p>Natural killer cells are lymphocytes that respond rapidly to intracellular pathogens or cancer/stressed cells by producing pro-inflammatory cytokines or chemokines and by killing target cells through direct cytolysis. NK cells are distinct from B and T lymphocytes in that they become activated through a series of broadly expressed germ line encoded activating and inhibitory receptors or through the actions of inflammatory cytokines. They are the founding member of the innate lymphoid cell family, which mirror the functions of T lymphocytes, with NK cells being the innate counterpart to CD8 T lymphocytes. Despite the functional relationship between NK cells and CD8 T cells, the mechanisms controlling their specification, differentiation and maturation are distinct, with NK cells emerging from multipotent lymphoid progenitors in the bone marrow under the control of a unique transcriptional program. Over the past few years, substantial progress has been made in understanding the developmental pathways and the factors involved in generating mature and functional NK cells. NK cells have immense therapeutic potential and understanding how to acquire large numbers of functional cells and how to endow them with potent activity to control hematopoietic and non-hematopoietic malignancies and autoimmunity is a major clinical goal. In this review, we examine basic aspects of conventional NK cell development in mice and humans and discuss multiple transcription factors that are known to guide the development of these cells.</p>","PeriodicalId":50862,"journal":{"name":"Advances in Immunology","volume":"146 ","pages":"1-28"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/bs.ai.2020.01.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37866014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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