Identification and characterization of T reg-like cells in zebrafish.

Identification and characterization of T reg-like cells in zebrafish.
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DOI:
10.1084/jem.20162084
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发表时间:
2017-12-04
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Ceol CJ
Ceol CJ
中科院分区:
其他
文献类型:
--
作者:
Kasheta M;Painter CA;Moore FE;Lobbardi R;Bryll A;Freiman E;Stachura D;Rogers AB;Houvras Y;Langenau DM;Ceol CJ

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Kasheta et al. report the identification of T reg–like cells in zebrafish, a means to track and live-image these cells, and foxp3a-deficient mutants that display lymphoproliferation, severe inflammation, and other hallmarks of T reg deficiency syndromes. Regulatory T (T reg) cells are a specialized sublineage of T lymphocytes that suppress autoreactive T cells. Functional studies of T reg cells in vitro have defined multiple suppression mechanisms, and studies of T reg–deficient humans and mice have made clear the important role that these cells play in preventing autoimmunity. However, many questions remain about how T reg cells act in vivo. Specifically, it is not clear which suppression mechanisms are most important, where T reg cells act, and how they get there. To begin to address these issues, we sought to identify T reg cells in zebrafish, a model system that provides unparalleled advantages in live-cell imaging and high-throughput genetic analyses. Using a FOXP3 orthologue as a marker, we identified CD4-enriched, mature T lymphocytes with properties of T reg cells. Zebrafish mutant for foxp3a displayed excess T lymphocytes, splenomegaly, and a profound inflammatory phenotype that was suppressed by genetic ablation of lymphocytes. This study identifies T reg–like cells in zebrafish, providing both a model to study the normal functions of these cells in vivo and mutants to explore the consequences of their loss.
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