Invariant TCR-triggered protein kinase D activation mediates NKT cell development

Ishikawa, Eri; Kosako, Hidetaka; Motooka, Daisuke et al.

The Journal of experimental medicine, 2025, 222(12), e20250541

アクセス数:91件（2026-02-15 21:36 集計）

固定URL: https://hdl.handle.net/11094/103494

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タイトル
Invariant TCR-triggered protein kinase D activation mediates NKT cell development
著者
NRID
1000020546478 1000020546478
ORCID
0000-0002-4922-6751 0000-0002-4922-6751
researchmap permalink
eishikawa eishikawa
Scopus Author ID
57219186766 57219186766
著者名
Ishikawa, Eri
NRID
1000010291171 1000010291171
著者名
Kosako, Hidetaka
NRID
1000010636830 1000010636830
researchmap permalink
daisukem daisukem
Scopus Author ID
35315737900 35315737900
著者名
Motooka, Daisuke
著者名
Imasaka, Mai
NRID
1000070415339 1000070415339
著者名
Watarai, Hiroshi
NRID
1000060398229 1000060398229
著者名
Ohmuraya, Masaki
NRID
1000040312946 1000040312946
ORCID
0000-0002-5184-6917 0000-0002-5184-6917
researchmap permalink
read0117961 read0117961
Scopus Author ID
57219186899 57219186899
著者名
Yamasaki, Sho
内容
Ishikawa E., Kosako H., Motooka D., et al. Invariant TCR-triggered protein kinase D activation mediates NKT cell development. The Journal of experimental medicine, 2025, 222, e20250541 (2025). https://doi.org/10.1084/jem.20250541
抄録
Development of invariant natural killer T (iNKT) cells in the thymus requires cell-cell interaction through invariant TCR (iTCR) and CD1d, which induces expression of the transcription factor, promyelocytic leukemia zinc finger (PLZF). However, the signaling pathway linking iTCR and PLZF remains unclear. Here, we report that a serine/threonine kinase, protein kinase D (PKD), plays a pivotal role in iNKT cell development. In T cell-specific PKD-deficient (Prkd2/3^∆CD4) mice, PLZF induction and iNKT cell generation were severely impaired, which were rescued by introduction of a PLZF transgene. We identified the transcription factor Ikaros as a substrate of PKD upon iTCR stimulation. Knock-in mice carrying a phosphorylation-defective mutant Ikaros (Ikzf1^S267/275A) exhibited an impairment of iNKT cell development, whereas conventional T cells were normal. In iNKT cells, Ikaros binds to the upstream region of the PLZF gene to induce its transcription. Mutant mice lacking the Ikaros-binding site (Zbtb16^∆IBS) generated fewer iNKT cells than WT mice. These results suggest that PKD links iTCRs to PLZF induction through Ikaros, thereby mediating iNKT cell development.
出版者
Rockefeller University Press
収録物名
The Journal of experimental medicine
巻(号)
222(12)
ページ
e20250541
刊行年月
2025-09-18
言語
英語
ハンドルURL
https://hdl.handle.net/11094/103494
eISSN
15409538
関連情報 (isIdenticalTo)
DOI (出版社版)
https://doi.org/10.1084/jem.20250541
アクセス権
open access
権利情報
© 2025 Ishikawa E., Kosako H., Motooka D., et al. Invariant TCR-triggered protein kinase D activation mediates NKT cell development. Originally published in The Journal of experimental medicine 222, e20250541 (2025); https://doi.org/10.1084/jem.20250541.
出版タイプ
Version of Record
カテゴリ
学術雑誌論文 Journal Article