Functional restoration of CD56(bright) NK cells facilitates immune control via IL-15 and NKG2D in patients under antiviral treatment for chronic hepatitis B.
Functional restoration of CD56(bright) NK cells facilitates immune control via IL-15 and NKG2D in patients under antiviral treatment for chronic hepatitis B.
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CD56bright NK 细胞的功能恢复有助于慢性乙型肝炎抗病毒治疗患者通过 IL-15 和 NKG2D 进行免疫控制
DOI：
10.1007/s12072-017-9803-4
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发表时间：
2017-09
影响因子：
6.6
通讯作者：
Ning Q
中科院分区：
文献类型：
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作者：
Chen T;Zhu L;Shi A;Ding L;Zhang X;Tan Z;Guo W;Yan W;Han M;Jia J;Luo X;Schuppan D;Ning Q
背景和目的B型肝炎病毒（HBV）具有内在免疫原性，在许多患者中具有持久的免疫控制。然而，有效的免疫控制的机制和关键的细胞类型是不完全understood.MethodsWe研究了自然杀伤（NK）细胞的数量和功能的恢复后抗病毒治疗的52例肝炎B e抗原（HBeAg）阳性慢性肝炎B（CH B）患者谁收到替比夫定（LdT）48周。分别于第0、12、24、36和48周采集血样，检测HBV DNA、乙肝B表面抗原（HBsAg）、HBeAg、肝酶和NK细胞参数。尤其是基线丙氨酸转氨酶（ALT）为正常值上限（ULN）2 - 5倍或HBV DNA< 9 log 10拷贝/ml的患者。CD 3 − CD 56 bright NK细胞上活化受体NKG 2D和NKp 46的表达（数量和密度）增强，而抑制性受体NKG 2A减少。值得注意的是，在HBeAg血清转换患者中，CD 3 − CD 56 bright或NKG 2D + CD 3 − CD 56 bright NK细胞的数量恢复明显更好。NK细胞活化血清白细胞介素15（IL-15）在LdT治疗期间显著升高，尤其是在HBeAg血清转换者中。LdT显着增强NKG 2D和IL-15的表达纯化的外周NK细胞从治疗初治HBeAg阳性CHB patients.ConclusionsFunctional恢复CD 56亮NK细胞通过上调IL-15和NKG 2D是一种新的活性LdT和其他可能的抗病毒药物，独立于其对HBV复制的影响。这也证明了宿主免疫恢复在控制慢性HBV感染中的重要性。
Background and aimsHepatitis B virus (HBV) is intrinsically immunogenic, with long-lasting immune control in many patients. However, the mechanisms and key cell types underlying effective immune control are incompletely understood.MethodsWe studied the restoration of natural killer (NK) cell numbers and function post antiviral treatment in 52 hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients who received telbivudine (LdT) for 48 weeks. Blood samples were collected at week 0, 12, 24, 36, and 48 and tested for HBV DNA, hepatitis B surface antigen (HBsAg), HBeAg, liver enzymes, and NK cell parameters.ResultsCompared with baseline, the number of peripheral CD3−CD56bright NK cells increased significantly from week 24 to 48, especially in patients with baseline alanine transaminase (ALT) two- to fivefold the upper line of normal (ULN) or HBV DNA <9 log10 copies/ml. Expression (number and density) of activating receptors NKG2D and NKp46 on CD3−CD56bright NK cells was enhanced, while inhibitory receptor NKG2A decreased. Notably, numbers of CD3−CD56bright or NKG2D+CD3−CD56bright NK cells were significantly better restored in patients with HBeAg seroconversion. NK cell activating serum interleukin 15 (IL-15) was significantly increased during LdT treatment, especially in HBeAg seroconverters. LdT significantly enhanced expression of NKG2D and IL-15 in cultures of purified peripheral NK cells from treatment-naïve HBeAg-positive CHB patients.ConclusionsFunctional restoration of CD56bright NK cells via upregulation of IL-15 and NKG2D is a novel activity of LdT and likely other antivirals, independent of its effect on HBV replication. This also demonstrates the importance of host immune restoration in controlling chronic HBV infection.
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影响因子：
29.4
作者：
El-Serag HB
通讯作者：
El-Serag HB
影响因子：
6.7
作者：
Peppa D;Micco L;Javaid A;Kennedy PT;Schurich A;Dunn C;Pallant C;Ellis G;Khanna P;Dusheiko G;Gilson RJ;Maini MK
通讯作者：
Maini MK
Interleukin-15 通过上调 NKG2D 和细胞毒性效应分子表达以及 STAT1 和 ERK1/2 磷酸化来提高自然杀伤细胞的细胞毒性
影响因子：
3.8
作者：
Zhang, Cai;Zhang, Jianhua;Tian, Zhigang
通讯作者：
Tian, Zhigang
慢性丙型肝炎病毒和丙型肝炎病毒感染的抗病毒治疗的免疫学方面。
DOI：
10.1002/hep.27323
发表时间：
2015-02
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Rehermann B;Bertoletti A
通讯作者：
Bertoletti A
影响因子：
9.1
作者：
TrehanPati, Nirupma;Kotillil, Shyam;Sarin, Shiv Kumar
通讯作者：
Sarin, Shiv Kumar