| 著者 |
Tahira, Yuki
幣, 光太郎
WEKO
24708
e-Rad_Researcher
20468028
| ja |
幣, 光太郎
宮崎大学
|
| ja-Kana |
シデ, コウタロウ
|
| en |
Shide, Kotaro
University of Miyazaki
|
Search repository
亀田, 拓郎
WEKO
7990
e-Rad_Researcher
30468029
| ja |
亀田, 拓郎
宮崎大学
|
| ja-Kana |
カメダ, タクロウ
|
| en |
Kameda, Takuro
University of Miyazaki
|
Search repository
内田, 泰介
WEKO
34201
| ja |
内田, 泰介
宮崎大学
|
| ja-Kana |
ウチダ, タイスケ
|
| en |
Uchida, Taisuke
University of Miyazaki
|
Search repository
上運天, 綾子
WEKO
24710
e-Rad_Researcher
30800750
| ja |
上運天, 綾子
宮崎大学
|
| ja-Kana |
カミウンテン, アヤコ
|
| en |
Kamiunten, Ayako
University of Miyazaki
|
Search repository
秋月, 渓一
WEKO
34678
e-Rad_Researcher
50975331
| ja |
秋月, 渓一
宮崎大学
|
| ja-Kana |
アキヅキ, ケイイチ
|
| en |
Akizuki, Keiichi
University of Miyazaki
|
Search repository
久冨木, 庸子
WEKO
7992
e-Rad_Researcher
00284836
| ja |
久冨木, 庸子
宮崎大学
|
| ja-Kana |
クブキ, ヨウコ
|
| en |
Kubuki, Yoko
University of Miyazaki
|
Search repository
Karasawa, Masayoshi
池田, 良磨
Matsumoto, Kengo
Bai, Jie
Terashima, Minoru
Kato, Koji
宇都, 倫史
WEKO
30185
e-Rad_Researcher
10624653
| ja |
宇都, 倫史
宮崎大学
|
| ja-Kana |
ウト, トモフミ
|
| en |
Uto, Tomofumi
University of Miyazaki
|
Search repository
深谷, 知宏
WEKO
30184
e-Rad_Researcher
20624323
| ja |
深谷, 知宏
宮崎大学
|
| ja-Kana |
フカヤ, トモヒロ
|
| en |
Fukaya, Tomohiro
University of Miyazaki
|
Search repository
三苫, 修也
WEKO
34689
e-Rad_Researcher
50911111
| ja |
三苫, 修也
宮崎大学
|
| ja-Kana |
ミトマ, シュウヤ
|
| en |
Mitoma, Shuya
University of Miyazaki
|
Search repository
佐藤, 克明
WEKO
30111
e-Rad_Researcher
40301147
| ja |
佐藤, 克明
宮崎大学
|
| ja-Kana |
サトウ, カツアキ
|
| en |
Sato, Katsuaki
University of Miyazaki
|
Search repository
上平, 雄大
WEKO
35020
| ja |
上平, 雄大
宮崎大学
|
| ja-Kana |
ウエヒラ, ユウダイ
|
| en |
Uehira, Yudai
University of Miyazaki
|
Search repository
上野, 浩晶
WEKO
33888
e-Rad_Researcher
00381062
| ja |
上野, 浩晶
宮崎大学
|
| ja-Kana |
ウエノ, ヒロアキ
|
| en |
Ueno, Hiroaki
University of Miyazaki
|
Search repository
Sashida, Goro
山口, 秀樹
WEKO
21852
e-Rad_Researcher
10305097
| ja |
山口, 秀樹
宮崎大学
|
| ja-Kana |
ヤマグチ, ヒデキ
|
| en |
Yamaguchi, Hideki
University of Miyazaki
|
Search repository
下田, 和哉
WEKO
7997
e-Rad_Researcher
90311844
| en |
Shimoda, Kazuya
University of Miyazaki
|
| ja |
下田, 和哉
宮崎大学
|
| ja-Kana |
シモダ, カズヤ
|
Search repository
|
|
内容記述 |
Interferon-α (IFN-α) exhibits antiviral and antiproliferative effects on normal and neoplastic cells. Intracellular signaling of IFN-α is mediated by tyrosine kinase 2 (TYK2) and janus kinase 1 (JAK1), followed by signal transducers and activators of transcription (STATs). TYK2 is redundant for the antiviral effect of IFN-α; however, the requirements for antiproliferative effects are unknown. We assessed the role of TYK2 in the effects of IFN-α in myeloproliferative neoplasm (MPN) model mice. Jak2V617F transgenic mice develop MPNs resembling human primary myelofibrosis, and ropeginterferon-α-2b ameliorated their features. However, these IFN-α effects were absent in Jak2V617F;Tyk2−/− mice. In mixed wild-type (WT)/Jak2V617F chimeric mice, IFN-α treatment induces Jak2V617F hematopoietic stem cells (HSCs) to enter the cell cycle and skew their differentiation into the megakaryocyte lineage, decreasing the number of Jak2V617F HSCs. The effects of IFN-α on Jak2V617F HSCs were not observed in mixed WT/Jak2V617F;Tyk2−/− mice, indicating that TYK2 is essential for the effects of IFN-α on both Jak2V617F progenitors and HSCs. The mechanism of IFN-α in Jak2V617F HSCs and progenitors differed: genes regulating the cell cycle were enriched in IFN-α–stimulated Jak2V617F HSCs, but not in Jak2V617F progenitors; genes regulating antiproliferation were enriched in IFN-α–stimulated Jak2V617F progenitors but not in Jak2V617F HSCs. The major IFN-α signaling molecule activated by JAKs is STAT1, which is essential for the antiviral effect. Most effects of IFN-α on Jak2V617F cells were preserved in Jak2V617F;Stat1−/− mice but to a moderate degree compared with Jak2V617F mice. Our study reveals essential roles of TYK2 for the preferential suppressive effect of IFN-α on Jak2V617F progenitors and HSCs. |
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