TRIM28 expression on dendritic cells prevents excessive T cell priming by silencing endogenous retrovirus

Shunsuke Chikuma, Soichiro Yamanaka, So Nakagawa, Mahoko Takahashi Ueda, Hodaka Hayabuchi, Yukiko Tokifuji, Masashi Kanayama, Tadashi Okamura, Hisashi Arase, Akihiko Yoshimura

研究成果: Article査読

3 被引用数 (Scopus)

抄録

Acquired immune reaction is initiated by dendritic cells (DCs), which present Ags to a few naive Ag-specific T cells. Deregulation of gene expression in DCs may alter the outcome of the immune response toward immunodeficiency and/or autoimmune diseases. Expression of TRIM28, a nuclear protein that mediates gene silencing through heterochromatin, decreased in DCs from old mice, suggesting alteration of gene regulation. Mice specifically lacking TRIM28 in DCs show increased DC population in the spleen and enhanced T cell priming toward inflammatory effector T cells, leading to acceleration and exacerbation in experimental autoimmune encephalomyelitis. TRIM28-deficient DCs were found to ectopically transcribe endogenous retrovirus (ERV) elements. Combined genome-wide analysis revealed a strong colocalization among the decreased repressive histone mark H3K9me3- transcribed ERV elements and the derepressed host genes that were related to inflammation in TRIM28-deficient DCs. This suggests that TRIM28 occupancy of ERV elements critically represses expression of proximal inflammatory genes on the genome. We propose that gene silencing through repressive histone modification by TRIM28 plays a role in maintaining the integrity of precise gene regulation in DCs, which prevents aberrant T cell priming to inflammatory effector T cells.

本文言語English
ページ(範囲)1529-1539
ページ数11
ジャーナルJournal of Immunology
206
7
DOI
出版ステータスPublished - 2021 4月 1

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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