Abstract:
:Transcriptional regulation of gene expression is a key component of orchestrating proper immune cell development and function. One strategy for maintaining these transcriptional programs has been the evolution of transcription factor families with members possessing overlapping functions. Using the germ line deletion of Snai2 combined with the hematopoietic specific deletion of Snai3, we report that these factors function redundantly to preserve the development of B and T cells. Such animals display severe lymphopenia, alopecia and dermatitis as well as profound autoimmunity manifested by the production of high levels of autoantibodies as early as 3 weeks of age and die by 30 days after birth. Autoantibodies included both IgM and IgG isotypes and were reactive against cytoplasmic and membranous components. A regulatory T cell defect contributed to the autoimmune response in that adoptive transfer of wild type regulatory T cells alleviated symptoms of autoimmunity. Additionally, transplantation of Snai2/Snai3 double deficient bone marrow into Snai2 sufficient Rag2(-/-) recipients resulted in autoantibody generation. The results demonstrated that appropriate expression of Snai2 and Snai3 in cells of hematopoietic derivation plays an important role in development and maintenance of immune tolerance.
journal_name
Cell Immunoljournal_title
Cellular immunologyauthors
Pioli PD,Chen X,Weis JJ,Weis JHdoi
10.1016/j.cellimm.2015.02.009subject
Has Abstractpub_date
2015-05-01 00:00:00pages
1-18issue
1eissn
0008-8749issn
1090-2163pii
S0008-8749(15)00043-Xjournal_volume
295pub_type
杂志文章abstract::The loss of thymic function with age may be due to diminished numbers of T-cell progenitors and the loss of critical mediators within the thymic microenvironment. To assess the molecular changes associated with this loss, we examined transcriptomes of progressively aging mouse thymi, of different sexes and on caloric-...
journal_title:Cellular immunology
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更新日期:1985-10-15 00:00:00
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更新日期:1984-11-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
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更新日期:1989-10-15 00:00:00
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更新日期:1985-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:1992-08-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
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更新日期:1993-03-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1016/j.cellimm.2006.05.005
更新日期:2006-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:1987-09-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
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更新日期:1983-07-15 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1006/cimm.2001.1837
更新日期:2001-08-25 00:00:00
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pub_type: 杂志文章
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更新日期:1990-10-15 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
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更新日期:1986-04-01 00:00:00
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更新日期:1984-08-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
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journal_title:Cellular immunology
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journal_title:Cellular immunology
pub_type: 杂志文章
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更新日期:1999-11-25 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
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更新日期:1983-01-01 00:00:00
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更新日期:1984-02-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
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更新日期:2011-01-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
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更新日期:1983-02-15 00:00:00
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pub_type: 杂志文章
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更新日期:1988-06-01 00:00:00