Restoration of type I interferon signaling in intrahepatically primed CD8+ T cells promotes functional differentiation
Restoration of type I interferon signaling in intrahepatically primed CD8+ T cells promotes functional differentiation
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肝内引发的 CD8 T 细胞中 I 型干扰素信号的恢复可促进功能分化
DOI：
10.1172/jci.insight.145761
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发表时间：
2021
期刊：
影响因子：
8
通讯作者：
Tanaka Yasuhito
中科院分区：
文献类型：
--
作者：
Kawashima Keigo;Isogawa Masanori;Onishi Masaya;Baudi Ian;Saito Satoru;Nakajima Atsushi;Fujita Takashi;Tanaka Yasuhito
B型肝炎病毒特异性（HBV特异性）CD 8 + T细胞在肝脏中引发后不能获得效应子功能，但对功能障碍的分子基础知之甚少。通过比较肝内启动的、功能障碍的HBV特异性CD 8 + T细胞与系统启动的、功能性效应物对应物的基因表达谱，我们发现干扰素刺激基因（ISG）的表达在功能障碍的CD 8 + T细胞中被选择性抑制。ISG抑制与IFN-α处理后STAT 1磷酸化受损相关。重要的是，肝脏中I型干扰素（IFN-1）的强烈诱导促进了肝内引发的HBV特异性CD 8 + T细胞的功能分化，这与T细胞中ISG表达的恢复有关。这些结果表明，肝内引发抑制CD 8 + T细胞中的IFN-I信号传导，这可能有助于功能障碍。数据还表明肝内IFN-1的稳健诱导对于治疗慢性HBV感染的治疗价值。
Hepatitis B virus–specific (HBV-specific) CD8+ T cells fail to acquire effector functions after priming in the liver, but the molecular basis for the dysfunction is poorly understood. By comparing the gene expression profile of intrahepatically primed, dysfunctional HBV-specific CD8+ T cells with that of systemically primed, functional effector counterparts, we found that the expression of interferon-stimulated genes (ISGs) is selectively suppressed in the dysfunctional CD8+ T cells. The ISG suppression was associated with impaired phosphorylation of STAT1 in response to IFN-α treatment. Importantly, a strong induction of type I interferons (IFN-Is) in the liver facilitated the functional differentiation of intrahepatically primed HBV-specific CD8+ T cells in association with the restoration of ISGs’ expression in the T cells. These results suggest that intrahepatic priming suppresses IFN-I signaling in CD8+ T cells, which may contribute to the dysfunction. The data also suggest a therapeutic value of the robust induction of intrahepatic IFN-Is for the treatment of chronic HBV infection.
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影响因子：
3.7
作者：
Hamada-Tsutsumi S;Iio E;Watanabe T;Murakami S;Isogawa M;Iijima S;Inoue T;Matsunami K;Tajiri K;Ozawa T;Kishi H;Muraguchi A;Joh T;Tanaka Y
通讯作者：
Tanaka Y
影响因子：
20.3
作者：
Gil, MP;Salomon, R;Biron, CA
通讯作者：
Biron, CA
DOI：
10.1073/pnas.0401771101
发表时间：
2004-04-27
影响因子：
11.1
作者：
Wieland, S;Thimme, R;Chisari, FV
通讯作者：
Chisari, FV
影响因子：
15.9
作者：
Dill, Michael T.;Makowska, Zuzanna;Heim, Markus H.
通讯作者：
Heim, Markus H.
影响因子：
29.4
作者：
Park JJ;Wong DK;Wahed AS;Lee WM;Feld JJ;Terrault N;Khalili M;Sterling RK;Kowdley KV;Bzowej N;Lau DT;Kim WR;Smith C;Carithers RL;Torrey KW;Keith JW;Levine DL;Traum D;Ho S;Valiga ME;Johnson GS;Doo E;Lok AS;Chang KM;Hepatitis B Research Network
通讯作者：
Hepatitis B Research Network