Current directions in autoimmunity最新文献_第8页

BLyS and B cell autoimmunity. BLyS和B细胞自身免疫

Current directions in autoimmunity Pub Date : 2003-01-01 DOI: 10.1159/000066854

Tong Zhou, Jun Zhang, Robert Carter, Robert Kimberly

引用次数: 25

Apoptosis and B cell tolerance. 凋亡与B细胞耐受。

Current directions in autoimmunity Pub Date : 2003-01-01 DOI: 10.1159/000066855

Jeffrey C Rathmell

引用次数: 10

Toll-like receptors and activation of autoreactive B cells. toll样受体和自身反应性B细胞的激活。

Current directions in autoimmunity Pub Date : 2003-01-01 DOI: 10.1159/000066858

Elizabeth A Leadbetter, Ian R Rifkin, Ann Marshak-Rothstein

引用次数: 66

Signaling mutations and autoimmunity. 信号突变和自身免疫

Current directions in autoimmunity Pub Date : 2003-01-01 DOI: 10.1159/000066856

Calvin C K Yu, Alusha A Mamchak, Anthony L DeFranco

{"title":"Signaling mutations and autoimmunity.","authors":"Calvin C K Yu, Alusha A Mamchak, Anthony L DeFranco","doi":"10.1159/000066856","DOIUrl":"https://doi.org/10.1159/000066856","url":null,"abstract":"<p><p>Mutations in a number of signaling components in mice can lead to strong autoimmune phenotypes. In some cases, these mutations likely compromise important feedback inhibitory pathways that downregulate antigen receptor signaling. For example, a deficiency of Lyn leads to a severe lupus-like autoimmunity. This autoimmunity may result from loss of a feedback inhibitory pathway in which Lyn phosphorylates CD22, triggering recruitment of the tyrosine phosphatase SHP-1 to the plasma membrane, which then dampens BCR signaling. Loss of Lyn also compromises an inhibitory pathway involving Fc gamma RIIb and SHIP, an inositol phosphatase. Mutation of Fyn exacerbates the autoimmunity caused by loss of Lyn. This may be due in part to a nonimmunological compromise in the integrity of the podocytes in the kidney, which may make the kidneys more susceptible to immune complex-induced damage. Fyn-deficient mice exhibit a number of immunological abnormalities and also exhibit some autoimmunity, although this is less severe than what is seen in Lyn-deficient mice. Recently a gain of function mutation in CD45 that may enhance activity of Src family tyrosine kinases has also been found to cause autoimmune disease, suggesting that the level of Src family tyrosine kinase activity is an important determinant of immune tolerance. Finally, several studies suggest that there is a significant interaction between Src family tyrosine kinases and the Fas pathway that is important for self-tolerance. Although these studies are still at an early stage, it seems clear that alterations in regulators of antigen receptor signaling can contribute to autoimmunity.</p>","PeriodicalId":81058,"journal":{"name":"Current directions in autoimmunity","volume":"6 ","pages":"61-88"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000066856","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22089508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 32

Abnormal B cell signal transduction in systemic lupus erythematosus. 系统性红斑狼疮患者B细胞信号转导异常。

Current directions in autoimmunity Pub Date : 2003-01-01 DOI: 10.1159/000066857

Islam U Khan, George C Tsokos, Gary M Kammer

引用次数: 16

TGF-beta: receptors, signaling pathways and autoimmunity. tgf - β:受体、信号通路和自身免疫。

Current directions in autoimmunity Pub Date : 2002-01-01 DOI: 10.1159/000060548

Wanjun Chen, S. Wahl

引用次数: 78

Interleukin-2 signaling and the maintenance of self-tolerance. 白细胞介素-2信号传导与自我耐受性的维持。

Current directions in autoimmunity Pub Date : 2002-01-01 DOI: 10.1159/000060549

B. Nelson

{"title":"Interleukin-2 signaling and the maintenance of self-tolerance.","authors":"B. Nelson","doi":"10.1159/000060549","DOIUrl":"https://doi.org/10.1159/000060549","url":null,"abstract":"IL-2 plays an important and complex role in the immune system, serving as a growth factor, a differentiation factor, and a regulator of cell death. It shares many of these functions with other cytokines such as IL-15, which complicates the interpretation of the IL-2-deficient phenotype. Nonetheless, it is clear that a major indispensable role of IL-2 signaling, at least in mice, is to limit the number of activated T cells in the periphery after exposure to self- or environmental antigens. Although we still do not understand the mechanism by which this occurs, there emerge several general conclusions that provide a foundation for future work on this issue. The autoimmune phenotype associated with IL-2 deficiency results from the dysregulated activity of thymus-derived TCR alpha beta CD4+ and/or CD8+ T cells. The process requires an initial antigenic stimulus (e.g., from intestinal flora or self-antigens), but can then spread to naive bystander T cells by an undefined mechanism. A key observation is that neighboring T cells with intact IL-2 signaling can suppress the dysregulated activity of IL-2- or IL-2R-deficient T cells in a dominant manner, indicating that IL-2-based immune regulation is a systemic rather than cell autonomous property. The IL-2R signal responsible for maintaining homeostasis is not dependent on either the Shc or Stat5 pathways, therefore AICD, which is Stat5-dependent in vitro, cannot be the critical mechanism. Finally, expression of the IL-2R in the thymus and not the periphery appears sufficient to suppress the autoimmune phenotype, suggesting that IL-2 signaling may be required for some aspect of thymocyte selection and/or differentiation that has so far gone undetected. These observations can be combined into a unified model wherein IL-2 signaling is required for the development of a regulatory T-cell subset that serves to terminate antigen-induced responses of TCR alpha beta T cells. On the other hand, the role of IL-2 in the maintenance of self-tolerance could be multifaceted, with no single model accounting for all experimental findings. Of note, most of our knowledge regarding IL-2 signaling and tolerance has come from studies of knockout mice. Conceptually, it is important to remember that the function of a molecule such as IL-2 is not simply the inverse of the phenotype seen when that molecule is absent, since necessity and sufficiency are not always coupled in physiological processes. In this regard, perhaps new insights into this important issue can be gained by better defining when and where IL-2 signaling normally occurs in wild-type animals and the functional status of the T cells involved.","PeriodicalId":81058,"journal":{"name":"Current directions in autoimmunity","volume":"5 1","pages":"92-112"},"PeriodicalIF":0.0,"publicationDate":"2002-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000060549","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65043465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 54

Abnormal T lymphocyte signal transduction in systemic lupus erythematosus. 系统性红斑狼疮患者T淋巴细胞信号转导异常。

Current directions in autoimmunity Pub Date : 2002-01-01 DOI: 10.1159/000060555

G. Kammer, G. Tsokos

引用次数: 16

Role of the B7-CD28/CTLA-4 pathway in autoimmune disease. B7-CD28/CTLA-4通路在自身免疫性疾病中的作用

Current directions in autoimmunity Pub Date : 2002-01-01 DOI: 10.1159/000060550

Tammy T. Chang, V. Kuchroo, A. Sharpe

引用次数: 47

Keeping the T-cell immune response in balance: role of protein tyrosine phosphatases in autoimmunity. 保持t细胞免疫反应平衡:蛋白酪氨酸磷酸酶在自身免疫中的作用。

Current directions in autoimmunity Pub Date : 2002-01-01 DOI: 10.1159/000060553

T. Mustelin

引用次数: 12