Defect in regulatory B-cell function and development of systemic autoimmunity in T-cell Ig mucin 1 (Tim-1) mucin domain-mutant mice

Xiao S.; Brooks C.R.; Zhu C.Wu C.Sweere J.M.Petecka S.Yeste A.Quintana F.J.Ichimura T.Sobel R.A.Bonventre J.V.Kuchroo V.K.

首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Defect in regulatory B-cell function and development of systemic autoimmunity in T-cell Ig mucin 1 (Tim-1) mucin domain-mutant mice

【24h】

Defect in regulatory B-cell function and development of systemic autoimmunity in T-cell Ig mucin 1 (Tim-1) mucin domain-mutant mice

机译：Defect in regulatory B-cell function and development of systemic autoimmunity in T-cell Ig mucin 1 (Tim-1) mucin domain-mutant mice

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相关主题

摘要

Tim-1, a type I transmembrane glycoprotein, consists of an IgV domain and a mucin domain. The IgV domain is essential for binding Tim-1 to its ligands, but little is known about the role of the mucin domain, even though genetic association of TIM-1 with atopy/asthma has been linked to the length of mucin domain. We generated a Tim-1-mutant mouse (Tim-1~(Δmucin)) in which the mucin domain was deleted genetically. The mutant mice showed a profound defect in IL-10 production from regulatory B cells (Bregs). Associated with the loss of IL-10 production in B cells, older Tim-1Δmucin mice developed spontaneous autoimmunity associated with hyperactive T cells, with increased production of IFN-γ and elevated serum levels of Ig and autoantibodies. However, Tim-1Δmucin mice did not develop frank systemic autoimmune disease unless they were crossed onto the Fas-mutant lpr mice on a C57BL/6 background. Tim-1Δmucinlpr mice developed accelerated and fulminant systemic autoimmunity with accumulation of abnormal double-negative T cells and autoantibodies to a number of lupus- associated autoantigens. Thus, Tim-1 plays a critical role in maintaining suppressive Breg function, and our data also demonstrate an unexpected role of the Tim-1 mucin domain in regulating Breg function and maintaining self-tolerance.

著录项

来源
《Proceedings of the National Academy of Sciences of the United States of America》 |2012年第30期|12105-12110|共6页
作者
Xiao S.; Brooks C.R.; Zhu C.Wu C.Sweere J.M.Petecka S.Yeste A.Quintana F.J.Ichimura T.Sobel R.A.Bonventre J.V.Kuchroo V.K.;
展开▼
作者单位

Center for Neurologic Disease, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States;

Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States;

Pathology and Laboratory Service, Veterans Affairs Health Care System, Palo Alto, CA 94304, United States;

展开▼
收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Hepatitis A virus cellular receptor 1; Inflammation; Kidney injury molecule 1;

Defect in regulatory B-cell function and development of systemic autoimmunity in T-cell Ig mucin 1 (Tim-1) mucin domain-mutant mice

摘要

著录项

相关主题

期刊订阅