期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 214, 期 11, 页码 3183-3195出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20171000
关键词
-
资金
- Medical Research Council Program Grant
- Biotechnology and Biological Sciences Research Council project
- Wellcome Trust Seed Award
- Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence PhD studentship
- BBSRC [BB/M006522/1] Funding Source: UKRI
- MRC [G9818340, MR/N000919/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/M006522/1] Funding Source: researchfish
- Medical Research Council [G9818340B, G9818340, 1407633, MR/N000919/1] Funding Source: researchfish
During alpha beta T cell development, the thymus medulla represents an essential microenvironment for T cell tolerance. This functional specialization is attributed to its typical organized topology consisting of a branching structure that contains medullary thymic epithelial cell (mTEC) networks to support negative selection and Foxp3(+) T-regulatory cell (T-reg) development. Here, by performing TEC-specific deletion of the thymus medulla regulator lymphotoxin beta receptor (LT beta R), we show that thymic tolerance mechanisms operate independently of LT beta R-mediated mTEC development and organization. Consistent with this, mTECs continue to express Fezf2 and Aire, regulators of intrathymic self-antigens, and support T-reg development despite loss of LT beta R-mediated medulla organogenesis. Moreover, we demonstrate that LT beta R controls thymic tolerance by regulating the frequency and makeup of intrathymic dendritic cells (DCs) required for effective thymocyte negative selection. In all, our study demonstrates that thymus medulla specialization for thymic tolerance segregates from medulla organogenesis and instead involves LT beta R-mediated regulation of the thymic DC pool.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据