The AP-1 transcription factor JunB is required for Th17 cell differentiation

Soh Yamazaki; Yoshihiko Tanaka; Hiromitsu Araki; Akira Kohda; Fumiyuki Sanematsu; Tomoko Arasaki; Xuefeng Duan; Fumihito Miura; Takaharu Katagiri; Ryodai Shindo; Hiroyasu Nakano; Takashi Ito; Yoshinori Fukui; Shogo Endo; Hideki Sumimoto

doi:10.1038/s41598-017-17597-3

The AP-1 transcription factor JunB is required for Th17 cell differentiation

Sci Rep. 2017 Dec 12;7(1):17402. doi: 10.1038/s41598-017-17597-3.

Authors

Soh Yamazaki^{1

2}, Yoshihiko Tanaka^{3

4}, Hiromitsu Araki¹, Akira Kohda¹, Fumiyuki Sanematsu³, Tomoko Arasaki⁵, Xuefeng Duan³, Fumihito Miura¹, Takaharu Katagiri², Ryodai Shindo², Hiroyasu Nakano², Takashi Ito¹, Yoshinori Fukui³, Shogo Endo⁵, Hideki Sumimoto⁶

Affiliations

¹ Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka, 812-8582, Japan.
² Department of Biochemistry, Toho University School of Medicine, Tokyo, 143-8540, Japan.
³ Division of Immunogenetics, Department of Immunobiology of Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan.
⁴ Section of Infection Biology, Department of Functional Bioscience, Fukuoka Dental College, Fukuoka, 814-0193, Japan.
⁵ Aging Neuroscience Research Team, Tokyo Metropolitan Institute of Gerontology, Tokyo, 173-0015, Japan.
⁶ Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka, 812-8582, Japan. hsumi@med.kyushu-u.ac.jp.

Abstract

Interleukin (IL)-17-producing T helper (Th17) cells are crucial for host defense against extracellular microbes and pathogenesis of autoimmune diseases. Here we show that the AP-1 transcription factor JunB is required for Th17 cell development. Junb-deficient CD4⁺ T cells are able to develop in vitro into various helper T subsets except Th17. The RNA-seq transcriptome analysis reveals that JunB is crucial for the Th17-specific gene expression program. Junb-deficient mice are completely resistant to experimental autoimmune encephalomyelitis, a Th17-mediated inflammatory disease, and naive T helper cells from such mice fail to differentiate into Th17 cells. JunB appears to activate Th17 signature genes by forming a heterodimer with BATF, another AP-1 factor essential for Th17 differentiation. The mechanism whereby JunB controls Th17 cell development likely involves activation of the genes for the Th17 lineage-specifying orphan receptors RORγt and RORα and reduced expression of Foxp3, a transcription factor known to antagonize RORγt function.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3T3 Cells
Animals
Basic-Leucine Zipper Transcription Factors / metabolism
Cell Differentiation / physiology*
Cell Line, Tumor
Encephalomyelitis, Autoimmune, Experimental / metabolism
Encephalomyelitis, Autoimmune, Experimental / pathology
Encephalomyelitis, Autoimmune, Experimental / prevention & control
HEK293 Cells
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism
Humans
Mice
Mice, Inbred C57BL
Mice, Transgenic
Nuclear Receptor Subfamily 1, Group F, Member 1 / metabolism
Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
Proto-Oncogene Proteins c-jun / metabolism
Psoriasis / metabolism
Psoriasis / pathology
Th17 Cells / metabolism*
Transcription Factors / genetics
Transcription Factors / metabolism*

Substances

Basic-Leucine Zipper Transcription Factors
Batf protein, mouse
Homeodomain Proteins
JunB protein, mouse
Meox2 protein, mouse
Nuclear Receptor Subfamily 1, Group F, Member 1
Nuclear Receptor Subfamily 1, Group F, Member 3
Proto-Oncogene Proteins c-jun
Rora protein, mouse
Rorc protein, mouse
Transcription Factors
junD protein, mouse