Self/nonself最新文献_第2页

A role of IL-1R1 signaling in the differentiation of Th17 cells and the development of autoimmune diseases. IL-1R1 信号在 Th17 细胞分化和自身免疫性疾病发展中的作用。

Self/nonself Pub Date : 2011-01-01 DOI: 10.4161/self.2.1.15639

Yonggang Sha, Silva Markovic-Plese

{"title":"A role of IL-1R1 signaling in the differentiation of Th17 cells and the development of autoimmune diseases.","authors":"Yonggang Sha, Silva Markovic-Plese","doi":"10.4161/self.2.1.15639","DOIUrl":"10.4161/self.2.1.15639","url":null,"abstract":"IL-1 cytokine family plays a key role in the innate immune response against pathogen- and danger-associated molecular patterns. More recently, IL-1 receptor type 1 (IL-R1) signaling has been identified as a critical step in the differentiation and commitment of Th17 cells, which mediate the development of autoimmune diseases. Given its significance in the induction of the adoptive immune response, this complex signaling pathway is tightly regulated. Upon binding of IL-1 to IL-1R1, IL-1R accessory protein (AcP) is recruited to form a high affinity IL-1R1-IL-1RAcP heterodimeric receptor, which initiates the downstream signaling cascade. Multiple negative regulators of this pathway, including inhibitory membrane-bound IL-RII, secreted soluble (s)IL-1RI, sIL-RII and sIL-1RAcP, the regulatory IL-1R1 antagonist (IL-1R1a) and the IL-1R1-signlaing-induced single Ig-IL-1R-related (SIGIRR), provide a negative feedback control of this pathway, and suppress excessive IL-1 signaling and Th17 cell differentiation. IL-1R1 signaling induces human Th17 cell differentiation, leading to the expression of IL-1R-associated protein kinase (IRAK)4 and retinoic acid-related orphan nuclear hormone receptor (ROR), Th17 cell lineage transcription factors, which together with signal transducer and activator of the transcription (STAT)3, activate this cell lineage's specific cytokine expression profile, including IL-17A, IL-17F, IL-21 and IL-22. Given the role of IL-1 signaling and Th17 cells in the development of the autoinflammatory and autoimmune diseases, therapeutic strategies inhibiting IL-1R1 signaling are discussed as a novel approach for the treatment of autoimmune diseases and particularly multiple sclerosis (MS).","PeriodicalId":89270,"journal":{"name":"Self/nonself","volume":"2 1","pages":"35-42"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136902/pdf/self0201_0035.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30020769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Searching for an effective, safe and universal anti-HIV vaccine: Finding the answer in just one short peptide. 寻找有效、安全和通用的抗艾滋病疫苗：只需一个短肽就能找到答案。

Self/nonself Pub Date : 2011-01-01 DOI: 10.4161/self.2.1.14762

Guglielmo Lucchese, Angela Stufano, Darja Kanduc

引用次数: 18

Differential occurrence of protein intrinsic disorder in the cytoplasmic signaling domains of cell receptors. 细胞受体胞质信号结构域中蛋白质内在紊乱的差异发生。

Self/nonself Pub Date : 2011-01-01 DOI: 10.4161/self.2.1.14790

Alexander B Sigalov, Vladimir N Uversky

{"title":"Differential occurrence of protein intrinsic disorder in the cytoplasmic signaling domains of cell receptors.","authors":"Alexander B Sigalov, Vladimir N Uversky","doi":"10.4161/self.2.1.14790","DOIUrl":"10.4161/self.2.1.14790","url":null,"abstract":"In human membrane proteins, intrinsically disordered regions, the regions that lack a well-defined three-dimensional structure under physiological conditions, preferentially occur in the cytoplasmic tails. Many of these proteins represent cell receptors that function by recognizing their cognate ligand outside the cell and translating this binding information into an intracellular activation signal. Based on location of recognition and signaling (effector) domains, functionally diverse and unrelated cell receptors can be classified into two main families: those in which binding and signaling domains are located on the same protein chain, the so-called single-chain receptors (SRs), and those in which these domains are intriguingly located on separate subunits, the so-called multichain receptors (MRs). Recognition domains of both SRs and MRs are known to be well ordered. In contrast, while cytoplasmic signaling domains of SRs are well-structured as well, those of MRs are intrinsically disordered. Despite important role of receptor signaling in health and disease, extensive comparative structural analysis of receptor signaling domains has not been carried out as of yet. In this study, using a variety of prediction algorithms, we show that protein disorder is a characteristic and distinctive feature of receptors with recognition and signaling functions distributed between separate protein chains. We also reveal that disorder distribution patterns are rather similar within SR subclasses suggesting potential functional explanations. Why did nature select protein disorder to provide intracellular signaling for MRs? Is there any correlation between disorder profiles of signaling domains and receptor function? These and other questions are addressed in this article.","PeriodicalId":89270,"journal":{"name":"Self/nonself","volume":"2 1","pages":"55-72"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136905/pdf/self0201_0055.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30020773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Kinetic proofreading and the search for nonself-peptides. 动态校对和非自肽的搜索。

Self/nonself Pub Date : 2011-01-01 DOI: 10.4161/self.2.1.15362

Andreas Jansson

引用次数: 11

Autoantibodies: Focus on anti-DNA antibodies. 自身抗体:专注于抗dna抗体。

Self/nonself Pub Date : 2011-01-01 DOI: 10.4161/self.2.1.15087

Nina Almqvist, Thomas H Winkler, Inga-Lill Mårtensson

引用次数: 14

MHC molecules in health and disease: At the cusp of a paradigm shift. 健康和疾病中的MHC分子:处于范式转变的尖端。

Self/nonself Pub Date : 2011-01-01 DOI: 10.4161/self.2.1.15757

Denise E de Almeida, Joseph Holoshitz

{"title":"MHC molecules in health and disease: At the cusp of a paradigm shift.","authors":"Denise E de Almeida, Joseph Holoshitz","doi":"10.4161/self.2.1.15757","DOIUrl":"https://doi.org/10.4161/self.2.1.15757","url":null,"abstract":"Half a century after the major histocompatibility complex (MHC) was discovered, its functional roles in health and disease remain poorly understood. Many hallmarks of the MHC, including its unusual evolution, structurefunction properties of its gene products and allele-specific associations with dozens of diseases and health traits cannot be convincingly explained by the tenets of existing paradigms. It is therefore becoming increasingly apparent that in order to better understand MHC-health/disease association-a phenomenon that impacts the health of millions-heterodox ideas are critically needed. Here we propose a testable, novel theory concerning the functional role of MHC molecules in health and disease. At the focus of this theory is an evolutionarily-conserved, tri-dimensional cusp-like prominence ('kink'), found in the midst of one of the two α helices that form the perimeter of the groove of all MHC molecules. Based on structural, functional and evolutionary considerations, as well as our recent experimental data, it is proposed here that the MHC cusp region is enriched in allele-specific signal transduction ligands that interact with non-MHC cell surface receptors and trigger signaling events. Aberrations in these pathways could lead to disease development, or affect the severity of such diseases.","PeriodicalId":89270,"journal":{"name":"Self/nonself","volume":"2 1","pages":"43-48"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/self.2.1.15757","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30020771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 35

Autoimmune mechanisms of scleroderma and a role of oxidative stress. 硬皮病的自身免疫机制和氧化应激的作用。

Self/nonself Pub Date : 2011-01-01 DOI: 10.4161/self.2.1.14058

Toshiyuki Yamamoto

引用次数: 27

Transplantation tolerance: Clinical potential of regulatory T cells. 移植耐受：调节性 T 细胞的临床潜力。

Self/nonself Pub Date : 2011-01-01 DOI: 10.4161/self.2.1.15422

Yannick D Muller, Jörg D Seebach, Leo H Bühler, Manuel Pascual, Dela Golshayan

{"title":"Transplantation tolerance: Clinical potential of regulatory T cells.","authors":"Yannick D Muller, Jörg D Seebach, Leo H Bühler, Manuel Pascual, Dela Golshayan","doi":"10.4161/self.2.1.15422","DOIUrl":"10.4161/self.2.1.15422","url":null,"abstract":"The major challenge in transplantation medicine remains long-term allograft acceptance, with preserved allograft function under minimal chronic immunosuppression. To safely achieve the goal of sustained donor-specific T and B cell non-responsiveness, research efforts are now focusing on therapies based on cell subsets with regulatory properties. In particular the transfusion of human regulatory T cells (Treg) is currently being evaluated in phase I/II clinical trials for the treatment of graft versus host disease following hematopoietic stem cell transplantation, and is also under consideration for solid organ transplantation. The purpose of this review is to recapitulate current knowledge on naturally occurring as well as induced human Treg, with emphasis on their specific phenotype, suppressive function and how these cells can be manipulated in vitro and/or in vivo for therapeutic purposes in transplantation medicine. We highlight the potential but also possible limitations of Treg-based strategies to promote long-term allograft survival. It is evident that the bench-to-beside translation of these protocols still requires further understanding of Treg biology. Nevertheless, current data already suggest that Treg therapy alone will not be sufficient and needs to be combined with other immunomodulatory approaches in order to induce allograft tolerance.","PeriodicalId":89270,"journal":{"name":"Self/nonself","volume":"2 1","pages":"26-34"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136901/pdf/self0201_0026.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30020770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Self and nonself recognition through C-type lectin receptor, Mincle. 通过c型凝集素受体的自我和非自我识别。

Self/nonself Pub Date : 2010-10-01 DOI: 10.4161/self.1.4.13736

Yasunobu Miyake, Eri Ishikawa, Tetsuaki Ishikawa, Sho Yamasaki

引用次数: 45

Unusual biophysics of immune signaling-related intrinsically disordered proteins. 免疫信号相关的内在紊乱蛋白的异常生物物理学。

Self/nonself Pub Date : 2010-10-01 DOI: 10.4161/self.1.4.13641

Alexander B Sigalov

{"title":"Unusual biophysics of immune signaling-related intrinsically disordered proteins.","authors":"Alexander B Sigalov","doi":"10.4161/self.1.4.13641","DOIUrl":"https://doi.org/10.4161/self.1.4.13641","url":null,"abstract":"Intrinsically disordered (ID) regions, the regions that lack a well-defined three-dimensional structure under physiological conditions, are preferentially located in the cytoplasmic segments of plasma membrane proteins, many of which are known to be involved in cell signaling. This is in line with our studies that demonstrated that cytoplasmic domains of signaling subunits of immune receptors, including those of ζ, CD3ε, CD3δ and CD3γ chains of T cell receptor, Igα and Igβ chains of B cell receptor as well as the Fc receptor γ chain represent a novel class of ID proteins (IDPs). The domains all have one or more copies of an immunoreceptor tyrosine-based activation motif, tyrosine residues of which are phosphorylated upon receptor engagement in an early and obligatory event in the signaling cascade. Our studies of these IDPs revealed several unusual biophysical phenomena, including (1) the specific dimerization of disordered protein molecules, (2) the fast and slow dimerization equilibrium, depending on the protein, (3) no disorder-to-order transition and the lack of significant chemical shift and peak intensity changes upon dimerization or interaction with a well-folded partner protein and (4) the dual mode of binding to model membranes (with and without folding), depending on the lipid bilayer stability. Here, I highlight several of these studies that not only facilitate a rethinking process of the fundamental paradigms in protein biophysics but also open new perspectives on the molecular mechanisms involved in receptor signaling.","PeriodicalId":89270,"journal":{"name":"Self/nonself","volume":"1 4","pages":"271-281"},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/self.1.4.13641","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29810730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12