Self/nonself最新文献_第3页

Development of a nanoparticulate formulation of retinoic acid that suppresses Th17 cells and upregulates regulatory T cells. 维甲酸纳米颗粒配方的开发，抑制Th17细胞和上调调节性T细胞。

Self/nonself Pub Date : 2010-10-01 DOI: 10.4161/self.1.4.13946

Noah A Capurso, Michael Look, Laura Jeanbart, Heba Nowyhed, Clara Abraham, Joe Craft, Tarek M Fahmy

{"title":"Development of a nanoparticulate formulation of retinoic acid that suppresses Th17 cells and upregulates regulatory T cells.","authors":"Noah A Capurso, Michael Look, Laura Jeanbart, Heba Nowyhed, Clara Abraham, Joe Craft, Tarek M Fahmy","doi":"10.4161/self.1.4.13946","DOIUrl":"https://doi.org/10.4161/self.1.4.13946","url":null,"abstract":"Retinoic acid (RA) is a small molecule capable of shunting developing T cells away from the Th17 lineage and towards the Treg phenotype, making it a potentially useful therapeutic for autoimmune and inflammatory diseases. However, therapy can be complicated by systemic toxicity and unpredictable bioavailability, making a targeted drug delivery vehicle for local therapy desirable. A promising approach is the use of nanoparticles, which have been demonstrated to increase potency and decrease toxicity of therapies in a variety of disease models including Th17 mediated diseases. Nanoparticles can also be targeted to specific cell types via surface modification, further increasing the potential specificity of this approach. We therefore constructed a nanoparticulate drug delivery platform from poly(lactic-co-glycolic acid) (PLGA) capable of encapsulating and releasing RA. Here we report the fabrication, characterization, and in vitro bioactivity of this platform. We demonstrate that RA containing PLGA nanoparticles suppress IL-17 production and ROR-γ(t) expression in T cells polarized towards the Th17 phenotype in vitro with similar potency to that of free drug. Furthermore, we show that these particles enhance TGF-β dependent Foxp3 expression and IL-10 production of T cells in vitro with similar potency to free RA. Finally, we demonstrate that T cells polarized towards the Th17 phenotype in the presence of free and nanoparticulate RA have similarly suppressed ability to induce IL-6 production by fibroblasts. Our findings demonstrate the feasibility of RA delivery via biodegradable nanoparticles and represent an exciting technology for the treatment of autoimmune and inflammatory diseases.","PeriodicalId":89270,"journal":{"name":"Self/nonself","volume":"1 4","pages":"335-340"},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/self.1.4.13946","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29698785","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: 21

Immunogenicity of protein therapeutics: The key causes, consequences and challenges. 蛋白质疗法的免疫原性:主要原因、后果和挑战。

Self/nonself Pub Date : 2010-10-01 DOI: 10.4161/self.1.4.13904

Matthew P Baker, Helen M Reynolds, Brooke Lumicisi, Christine J Bryson

引用次数: 284

The SCHOOL of nature: IV. Learning from viruses. 大自然的学校IV.向病毒学习

Self/nonself Pub Date : 2010-10-01 DOI: 10.4161/self.1.4.13279

Alexander B Sigalov

{"title":"The SCHOOL of nature: IV. Learning from viruses.","authors":"Alexander B Sigalov","doi":"10.4161/self.1.4.13279","DOIUrl":"10.4161/self.1.4.13279","url":null,"abstract":"During the co-evolution of viruses and their hosts, the latter have equipped themselves with an elaborate immune system to defend themselves from the invading viruses. In order to establish a successful infection, replicate and persist in the host, viruses have evolved numerous strategies to counter and evade host antiviral immune responses as well as exploit them for productive viral replication. These strategies include those that modulate signaling mediated by cell surface receptors. Despite tremendous advancement in recent years, the exact molecular mechanisms underlying these critical points in viral pathogenesis remain unknown. In this work, based on a novel platform of receptor signaling, the Signaling Chain HOmoOLigomerization (SCHOOL) platform, I suggest specific mechanisms used by different viruses such as human immunodeficiency virus (HIV), cytomegalovirus (CMV), severe acute respiratory syndrome coronavirus, human herpesvirus 6 and others, to modulate receptor signaling. I also use the example of HIV and CMV to illustrate how two unrelated enveloped viruses use a similar SCHOOL mechanism to modulate the host immune response mediated by two functionally different receptors: T cell antigen receptor and natural killer cell receptor, NKp30. This suggests that it is very likely that similar general mechanisms can be or are used by other viral and possibly non-viral pathogens. Learning from viruses how to target cell surface receptors not only helps us understand viral strategies to escape from the host immune surveillance, but also provides novel avenues in rational drug design and the development of new therapies for immune disorders.","PeriodicalId":89270,"journal":{"name":"Self/nonself","volume":"1 4","pages":"282-298"},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3062383/pdf/self0104_0282.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29810732","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

Role of defective autophagia and the intestinal flora in Crohn disease. 缺陷性自噬和肠道菌群在克罗恩病中的作用。

Self/nonself Pub Date : 2010-10-01 DOI: 10.4161/self.1.4.13990

Anouk Regeling, Rajesh Somasundaram, Colin de Haar, C Janneke van der Woude, Henri Braat, Maikel P Peppelenbosch

{"title":"Role of defective autophagia and the intestinal flora in Crohn disease.","authors":"Anouk Regeling, Rajesh Somasundaram, Colin de Haar, C Janneke van der Woude, Henri Braat, Maikel P Peppelenbosch","doi":"10.4161/self.1.4.13990","DOIUrl":"https://doi.org/10.4161/self.1.4.13990","url":null,"abstract":"The precise mechanisms underlying the development of Crohn disease (CD) remain controversial, but sufficient data have been collected to suggest that an uncontrolled immune response within the intestinal mucosa leads to inflammation in a genetically susceptible host. Although lack of mucosal regulatory T cells causes colitis in humans and experimental rodents, patients with CD have more rather than less regulatory activity in the intestine, apparently excluding defects in tolerance as the cause of CD. Genome-wide association studies have identified many gene variants that confer susceptibility and which seem associated to diminished functioning of especially innate immunity. In apparent agreement, CD patients are impaired with respect to innate immune responses and controlling bacterial flora in the intestine. Furthermore, severe genetic deficiencies in innate immunity, like e.g., lack of NADP oxidase activity or diminished function of the Wiskott Aldrich syndrome protein are associated with colitis in mice and men, and are often mistakenly diagnosed as CD. Thus we favor the view that the primary defect in CD is a lack in innate immunity, causing second tier immunological defenses to combat otherwise easily controlled bacterial breaches of the mucosal barrier.","PeriodicalId":89270,"journal":{"name":"Self/nonself","volume":"1 4","pages":"323-327"},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/self.1.4.13990","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29698786","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: 7

No human protein is exempt from bacterial motifs, not even one. 没有一种人类蛋白质可以不受细菌基序的影响，甚至一个都不能。

Self/nonself Pub Date : 2010-10-01 DOI: 10.4161/self.1.4.13315

Brett Trost, Guglielmo Lucchese, Angela Stufano, Mik Bickis, Anthony Kusalik, Darja Kanduc

{"title":"No human protein is exempt from bacterial motifs, not even one.","authors":"Brett Trost, Guglielmo Lucchese, Angela Stufano, Mik Bickis, Anthony Kusalik, Darja Kanduc","doi":"10.4161/self.1.4.13315","DOIUrl":"https://doi.org/10.4161/self.1.4.13315","url":null,"abstract":"The hypothesis that mimicry between a self and a microbial peptide antigen is strictly related to autoimmune pathology remains a debated concept in autoimmunity research. Clear evidence for a causal link between molecular mimicry and autoimmunity is still lacking. In recent studies we have demonstrated that viruses and bacteria share amino acid sequences with the human proteome at such a high extent that the molecular mimicry hypothesis becomes questionable as a causal factor in autoimmunity. Expanding upon our analysis, here we detail the bacterial peptide overlapping to the human proteome at the penta-, hexa-, hepta- and octapeptide levels by exact peptide matching analysis and demonstrate that there does not exist a single human protein that does not harbor a bacterial pentapeptide or hexapeptide motif. This finding suggests that molecular mimicry between a self and a microbial peptide antigen cannot be assumed as a basis for autoimmune pathologies. Moreover, the data are discussed in relation to the microbial immune escape phenomenon and the possible vaccine-related autoimmune effects.","PeriodicalId":89270,"journal":{"name":"Self/nonself","volume":"1 4","pages":"328-334"},"PeriodicalIF":0.0,"publicationDate":"2010-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/self.1.4.13315","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29698784","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: 75

Immunopathogenesis of inflammatory bowel disease. 炎症性肠病的免疫发病机制。

Self/nonself Pub Date : 2010-10-01 DOI: 10.4161/self.1.4.13560

Julien Matricon, Nicolas Barnich, Denis Ardid

引用次数: 127

Triggering receptor expressed on myeloid cells-1 as a new therapeutic target during inflammatory diseases. 髓细胞上表达的触发受体-1作为炎症性疾病的新治疗靶点。

Self/nonself Pub Date : 2010-07-01 Epub Date: 2010-07-02 DOI: 10.4161/self.1.3.12891

Marc Derive, Frédéric Massin, Sébastien Gibot

引用次数: 38

The self/nonself issue: A confrontation between proteomes. 自我/非自我问题:蛋白质组之间的对抗。

Self/nonself Pub Date : 2010-07-01 Epub Date: 2010-01-29 DOI: 10.4161/self.1.3.11897

Darja Kanduc

引用次数: 45

Gene therapy in diabetes. 糖尿病的基因治疗。

Self/nonself Pub Date : 2010-07-01 Epub Date: 2010-06-09 DOI: 10.4161/self.1.3.12643

Mary S Wong, Wayne J Hawthorne, Nicholas Manolios

引用次数: 22

The autoimmunity-related GIMAP5 GTPase is a lysosome-associated protein. 自身免疫相关的GIMAP5 GTPase是一种溶酶体相关蛋白。

Self/nonself Pub Date : 2010-07-01 Epub Date: 2010-06-25 DOI: 10.4161/self.1.3.12819

Vivian Wy Wong, Amy E Saunders, Amanda Hutchings, John C Pascall, Christine Carter, Nicholas A Bright, Simon A Walker, Nicholas T Ktistakis, Geoffrey W Butcher

{"title":"The autoimmunity-related GIMAP5 GTPase is a lysosome-associated protein.","authors":"Vivian Wy Wong, Amy E Saunders, Amanda Hutchings, John C Pascall, Christine Carter, Nicholas A Bright, Simon A Walker, Nicholas T Ktistakis, Geoffrey W Butcher","doi":"10.4161/self.1.3.12819","DOIUrl":"https://doi.org/10.4161/self.1.3.12819","url":null,"abstract":"A mutation in the rat GIMAP5 gene predisposes for autoimmunity, most famously in the BB rat model of autoimmune type 1 diabetes mellitus. This mutation is associated with severe peripheral T lymphopenia, as is mutation of the same gene in mice, but the mechanism by which GIMAP5 normally protects T cells from death is unknown. GIMAP5 is a putative small GTPase, a class of proteins which often fulfil their functions in the vicinity of cellular membranes. The objective of this study was to determine the normal intracellular location of GIMAP5 in lymphoid cells. Combining studies in rat, mouse and human systems, novel monoclonal antibodies (mAbs) were used to examine the localization of GIMAP5 and the closely-related protein, GIMAP1, in lymphoid cells by means of confocal microscopy and sub-cellular fractionation combined with immunoblotting. Additionally, human Jurkat T cells that inducibly express epitope-tagged GIMAP5 were established and used in electron microscopy (EM). Endogenous GIMAP5 was found to be located in a membraneous compartment/s which was also detected by established markers of lysosomes. GIMAP1, by contrast, was found to be located in the Golgi apparatus. EM studies of the inducible Jurkat T cells also found GIMAP5 in lysosomes and, in addition, in multivesicular bodies. This study establishes that the endogenous location of GIMAP5 is in lysosomes and related compartments and provides a clearer context for hypotheses about its mechanism of action.","PeriodicalId":89270,"journal":{"name":"Self/nonself","volume":"1 3","pages":"259-268"},"PeriodicalIF":0.0,"publicationDate":"2010-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/self.1.3.12819","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29810376","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: 38