KCTD9 contributes to liver injury through NK cell activation during hepatitis B virus-induced acute-on-chronic liver failure

被引：33

作者：

Chen, Tao ^{[1
]}

Zhu, Lin ^{[1
]}

Zhou, Yaoyong ^{[1
]}

Pi, Bin ^{[1
]}

Liu, Xiaojuan ^{[1
]}

Deng, Guohong ^{[2
]}

Zhang, Rong ^{[2
]}

Wang, Yuming ^{[2
]}

Wu, Zeguang ^{[1
]}

Han, Meifang ^{[1
]}

Luo, Xiaoping ^{[3
]}

Ning, Qin ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept & Inst Infect Dis, Wuhan 430030, Peoples R China

[2] Third Mil Med Univ, Southwest Hosp, Dept Infect Dis, Chongqing, Peoples R China

[3] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Pediat Dis, Wuhan 430030, Peoples R China

来源：

CLINICAL IMMUNOLOGY | 2013年 / 146卷 / 03期

基金：

美国国家科学基金会;

关键词：

KCTD9; Natural killer cell; HBV; Virus induced liver injury; Acute on chronic liver failure; T-CELLS; RECEPTOR; MECHANISMS; CYTOMEGALOVIRUS; TRANSDUCTION; RECOGNITION; INFECTION; DISEASE; PROTEIN; NKG2D;

D O I：

10.1016/j.clim.2012.12.013

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

We explored the expression of a newly identified potassium channel tetramerisation domain containing 9 (KCTD9) protein in 113 blood and 81 liver samples, from patients with mild chronic hepatitis B (CHB) or HBV-induced acute-on-chronic liver failure (HBV-ACLF). KCTD9 was highly expressed in peripheral and hepatic NK cells from HBV-ACLF patients compared with mild CHB patients, and this correlated positively with the severity of liver injury. The role of KCTD9 was further investigated in NK92 cells in vitro. KCTD9 overexpressed NK92 cells exhibited a marked increase in CD69 expression, cytotoxicity, IFN-gamma secretion and a significant decrease in NKG2A receptor expression. Inhibition of KCTD9 by shRNA resulted in reduced cytotoxic function. These results suggest the involvement of KCTD9 in NK cell activation and provide additional insight into a potential therapeutic target for molecular manipulation for HBV-ACLF patients. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：207 / 216

页数：10

共 48 条

[21] NK cell receptors [J].

Lanier, LL .

ANNUAL REVIEW OF IMMUNOLOGY, 1998, 16 :359-393

[22] Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells [J].

Lanier, LL ;

Corliss, BC ;

Wu, J ;

Leong, C ;

Phillips, JH .

NATURE, 1998, 391 (6668) :703-707

[23] Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures [J].

Lavanchy, D .

JOURNAL OF VIRAL HEPATITIS, 2004, 11 (02) :97-107

[24] Hepatitis B: The Virus and Disease [J].

Liang, T. Jake .

HEPATOLOGY, 2009, 49 (05) :S13-S21

[25] IL-2 receptor signaling through the Shb adapter protein in T and NK cells [J].

Lindholm, CK .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 296 (04) :929-936

[26] Interleukin-10 Is Expressed in HepG2.2.15 Cells and Regulated by STAT1 Pathway [J].

Liu, Min ;

Hao, Youhua ;

Ding, Honghui ;

Yang, Dongliang ;

Lu, Mengji .

JOURNAL OF HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY-MEDICAL SCIENCES, 2011, 31 (05) :625-631

[27] NK cells cause liver injury and facilitate the induction of T cell-mediated immunity to a viral liver infection [J].

Liu, ZX ;

Govindarajan, S ;

Okamoto, S ;

Dennert, G .

JOURNAL OF IMMUNOLOGY, 2000, 164 (12) :6480-6486

[28] The role of virus-specific CD8+ cells in liver damage and viral control during persistent hepatitis B virus infection [J].

Maini, MK ;

Boni, C ;

Lee, CK ;

Larrubia, JR ;

Reignat, S ;

Ogg, GS ;

King, AS ;

Herberg, J ;

Gilson, R ;

Alisa, A ;

Williams, R ;

Vergani, D ;

Naoumov, NV ;

Ferrari, C ;

Bertoletti, A .

JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (08) :1269-1280

[29] Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells [J].

Mandelboim, O ;

Lieberman, N ;

Lev, M ;

Paul, L ;

Arnon, TI ;

Bushkin, Y ;

Davis, DM ;

Strominger, JL ;

Yewdell, JW ;

Porgador, A .

NATURE, 2001, 409 (6823) :1055-1060

[30] Successful transduction of liver in hemophilia by AAV-factor IX and limitations imposed by the host immune response [J].

Manno, CS ;

Arruda, VR ;

Pierce, GF ;

Glader, B ;

Ragni, M ;

Rasko, J ;

Ozelo, MC ;

Hoots, K ;

Blatt, P ;

Konkle, B ;

Dake, M ;

Kaye, R ;

Razavi, M ;

Zajko, A ;

Zehnder, J ;

Nakai, H ;

Chew, A ;

Leonard, D ;

Wright, JF ;

Lessard, RR ;

Sommer, JM ;

Tigges, M ;

Sabatino, D ;

Luk, A ;

Jiang, HY ;

Mingozzi, F ;

Couto, L ;

Ertl, HC ;

High, KA ;

Kay, MA .

NATURE MEDICINE, 2006, 12 (03) :342-347

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