Thymic involution perturbs negative selection leading to autoreactive T cells that induce chronic inflammation

doi:10.4049/jimmunol.1500082

科研成果详情

题名	Thymic involution perturbs negative selection leading to autoreactive T cells that induce chronic inflammation
作者	Coder, Brandon D.1; Wang, Hongjun 2; Ruan, Linhui3; Su, Dong-Ming 1
发表日期	2015-06-15
发表期刊	Journal of Immunology 影响因子和分区
语种	英语
原始文献类型	Article
摘要	Thymic involution and the subsequent amplified release of autoreactive T cells increase the susceptibility toward developing autoimmunity, but whether they induce chronic inflammation with advanced age remains unclear. The presence of chronic low-level proinflammatory factors in elderly individuals (termed inflammaging) is a significant risk factor for morbidity and mortality in virtually every chronic age-related disease. To determine how thymic involution leads to the persistent release and activation of autoreactive T cells capable of inducing inflammaging, we used a Foxn1 conditional knockout mouse model that induces accelerated thymic involution while maintaining a young periphery. We found that thymic involution leads to T cell activation shortly after thymic egress, which is accompanied by a chronic inflammatory phenotype consisting of cellular infiltration into non- lymphoid tissues, increased TNF-α production, and elevated serum IL-6. Autoreactive T cell clones were detected in the periphery of Foxn1 conditional knockout mice. A failure of negative selection, facilitated by decreased expression of Aire rather than impaired regulatory T cell generation, led to autoreactive T cell generation. Furthermore, the young environment can reverse age-related regulatory T cell accumulation in naturally aged mice, but not inflammatory infiltration. Taken together, these findings identify thymic involution and the persistent activation of autoreactive T cells as a contributing source of chronic inflammation (inflammaging).
资助项目	National Institute on Aging[3R01AI081995-03S1];
出版者	American Association of Immunologists
ISSN	0022-1767
EISSN	1550-6606
卷号	194 期号:12 页码:5825-5837
DOI	10.4049/jimmunol.1500082
收录类别	SCOPUS
URL	查看原文
PubMed ID	25957168
SCOPUSEID	2-s2.0-84931418361
通讯作者地址	[Su, Dong-Ming]Department of Cell Biology and Immunology,University of North Texas Health Science Center at Fort Worth,3500 Camp Bowie Boulevard,Fort Worth,76107,United States
Scopus学科分类	Immunology and Allergy;Immunology
引用统计	被引频次：64[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/98197
专题	附属第一医院
通讯作者	Su, Dong-Ming
作者单位	1.Department of Cell Biology and Immunology,University of North Texas,Health Science Center at Fort Worth,3500 Camp Bowie Boulevard,Fort Worth,76107,United States; 2.Department of Histology and Embryology,Jilin Medical College,Jilin,China; 3.First Affiliated Hospital,Wenzhou Medical University,Wenzhou,China
推荐引用方式 GB/T 7714	Coder, Brandon D.,Wang, Hongjun,Ruan, Linhui,et al. Thymic involution perturbs negative selection leading to autoreactive T cells that induce chronic inflammation[J]. Journal of Immunology,2015,194(12):5825-5837.
APA	Coder, Brandon D., Wang, Hongjun, Ruan, Linhui, & Su, Dong-Ming. (2015). Thymic involution perturbs negative selection leading to autoreactive T cells that induce chronic inflammation. Journal of Immunology, 194(12), 5825-5837.
MLA	Coder, Brandon D.,et al."Thymic involution perturbs negative selection leading to autoreactive T cells that induce chronic inflammation".Journal of Immunology 194.12(2015):5825-5837.