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Language(s):
eng - English
Dates:
2013-04
Publication Status:
Issued
Pages:
14
Publishing info:
-
Table of Contents:
The Roquin-1 protein binds to messenger RNAs
(mRNAs) and regulates gene expression posttranscriptionally.
A single point mutation in Roquin-1,
but not gene ablation, increases follicular helper T
(Tfh) cell numbers and causes lupus-like autoimmune
disease in mice. In T cells, we did not identify
a unique role for the much lower expressed paralog
Roquin-2. However, combined ablation of both
genes induced accumulation of T cells with an
effector and follicular helper phenotype. We showed
that Roquin-1 and Roquin-2 proteins redundantly
repressed the mRNA of inducible costimulator
(Icos) and identified the Ox40 costimulatory receptor
as another shared mRNA target. Combined acute
deletion increased Ox40 signaling, as well as Irf4
expression, and imposed Tfh differentiation on
CD4+ T cells. These data imply that both proteins
maintain tolerance by preventing inappropriate
T cell activation and Tfh cell differentiation, and that
Roquin-2 compensates in the absence of Roquin-1,
but not in the presence of its mutated form.
Rev. Type:
Peer
Degree:
-
