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The E3 ubiquitin ligase GRAIL regulates T cell tolerance and regulatory T cell function by mediating T cell receptor-CD3 degradation.

Abstract：

:T cell activation is tightly regulated to avoid autoimmunity. Gene related to anergy in lymphocytes (GRAIL, encoded by Rnf128) is an E3 ubiquitin ligase associated with T cell tolerance. Here, we generated and analyzed GRAIL-deficient mice and found they were resistant to immune tolerance induction and exhibited greater susceptibility to autoimmune diseases than wild-type mice. GRAIL-deficient naive T cells, after activation, exhibited increased proliferation and cytokine expression than controls and did not depend on costimulation for effector generation. Moreover, GRAIL-deficient regulatory T (Treg) cells displayed reduced suppressive function, associated with increased Th17 cell-related gene expression. GRAIL-deficient naive and Treg cells were less efficient in downregulating T cell receptor (TCR)-CD3 expression after activation and exhibited increased NFATc1 transcription factor expression; GRAIL expression promoted CD3 ubiquitinylation. Our results indicate that GRAIL, by mediating TCR-CD3 degradation, regulates naive T cell tolerance induction and Treg cell function.

journal_name

Immunity

journal_title

Immunity

authors

Nurieva RI,Zheng S,Jin W,Chung Y,Zhang Y,Martinez GJ,Reynolds JM,Wang SL,Lin X,Sun SC,Lozano G,Dong C

doi

10.1016/j.immuni.2010.05.002

subject

Has Abstract

pub_date

2010-05-28 00:00:00

pages

670-80

issue

5

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(10)00168-8

journal_volume

32

pub_type

杂志文章

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