TY - JOUR
T1 - JunB regulates homeostasis and suppressive functions of effector regulatory T cells
AU - Koizumi, Shin ichi
AU - Sasaki, Daiki
AU - Hsieh, Tsung Han
AU - Taira, Naoyuki
AU - Arakaki, Nana
AU - Yamasaki, Shinichi
AU - Wang, Ke
AU - Sarkar, Shukla
AU - Shirahata, Hiroki
AU - Miyagi, Mio
AU - Ishikawa, Hiroki
N1 - Funding Information:
We thank Dr. Steven D. Aird for editing the manuscript. We also thank our laboratory members and Dr. Taku Kureha for valuable discussions. This work was supported by KAKENHI grant (16K19164, 18K15201, 18K15200) and by OIST Graduate University.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-018-07735-4
DO - 10.1038/s41467-018-07735-4
M3 - Article
C2 - 30559442
AN - SCOPUS:85058732417
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5344
ER -