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Nat Commun. 2018 Dec 17;9(1):5344. doi: 10.1038/s41467-018-07735-4.

JunB regulates homeostasis and suppressive functions of effector regulatory T cells.

Author information

1
Immune Signal Unit, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Okinawa, 904-0495, Japan.
2
DNA Sequencing Section, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Okinawa, 904-0495, Japan.
3
Immune Signal Unit, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Okinawa, 904-0495, Japan. hiroki.ishikawa@oist.jp.

Abstract

Foxp3-expressing CD4+ regulatory T (Treg) cells need to differentiate into effector Treg (eTreg) cells to maintain immune homeostasis. T-cell receptor (TCR)-dependent induction of the transcription factor IRF4 is essential for eTreg differentiation, but how IRF4 activity is regulated in Treg cells is still unclear. Here we show that the AP-1 transcription factor, JunB, is expressed in eTreg cells and promotes an IRF4-dependent transcription program. Mice lacking JunB in Treg cells develop multi-organ autoimmunity, concomitant with aberrant activation of T helper cells. JunB promotes expression of Treg effector molecules, such as ICOS and CTLA4, in BATF-dependent and BATF-independent manners, and is also required for homeostasis and suppressive functions of eTreg. Mechanistically, JunB facilitates the accumulation of IRF4 at a subset of IRF4 target sites, including those located near Icos and Ctla4. Thus, JunB is a critical regulator of IRF4-dependent Treg effector programs, highlighting important functions for AP-1 in Treg-mediated immune homeostasis.

PMID:
30559442
PMCID:
PMC6297218
DOI:
10.1038/s41467-018-07735-4
[Indexed for MEDLINE]
Free PMC Article

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