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Ssu72 is a T-cell receptor-responsive modifier that is indispensable for regulatory T cells

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Abstract
The homeostatic balance between effector T cells and regulatory T cells (Tregs) is crucial for adaptive immunity; however, epigenetic programs that inhibit phosphorylation to regulate Treg development, peripheral expression, and suppressive activity are elusive. Here, we found that the Ssu72 phosphatase is activated by various T-cell receptor signaling pathways, including the T-cell receptor and IL-2R pathways, and localizes at the cell membrane. Deletion of Ssu72 in T cells disrupts CD4(+) T-cell differentiation into Tregs in the periphery via the production of high levels of the effector cytokines IL-2 and IFN gamma, which induce CD4(+) T-cell activation and differentiation into effector cell lineages. We also found a close correlation between downregulation of Ssu72 and severe defects in mucosal tolerance in patients. Interestingly, Ssu72 forms a complex with PLC gamma 1, which is an essential effector molecule for T-cell receptor signaling as well as Treg development and function. Ssu72 deficiency impairs PLC gamma 1 downstream signaling and results in failure of Foxp3 induction. Thus, our studies show that the Ssu72-mediated cytokine response coordinates the differentiation and function of Treg cells in the periphery.
Author(s)
Jin-Kwan LeeSeo-Young KooHye-Mi NamJee-Boong LeeJiwon KoKyung-Mo KimEun-Ji ParkTae Jin KimHo Lee고현정Chang-Woo Lee
Issued Date
2021
Type
Article
Keyword
AutoimmunityFoxP3Regulatory T cellsSsu72T cell receptor
DOI
10.1038/s41423-021-00671-2
URI
https://oak.ulsan.ac.kr/handle/2021.oak/7972
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8166877&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Ssu72%20is%20a%20T-cell%20receptor-responsive%20modifier%20that%20is%20indispensable%20for%20regulatory%20T%20cells&offset=0&pcAvailability=true
Publisher
CELLULAR MOLECULAR IMMUNOLOGY
Location
중국
Language
영어
ISSN
1672-7681
Citation Volume
18
Citation Number
6
Citation Start Page
1395
Citation End Page
1411
Appears in Collections:
Medicine > Medicine
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