白细胞介素10对慢性乙型肝炎患者自然杀伤细胞的调控作用

周亮; 李小燕; 黄月华

doi:10.3969/j.issn.1001-5256.2016.08.040

白细胞介素10对慢性乙型肝炎患者自然杀伤细胞的调控作用

DOI: 10.3969/j.issn.1001-5256.2016.08.040

中山大学附属第三医院肝病实验室

基金项目:

国家重大科技专项-艾滋病和病毒性肝炎等重大传染病防治专项资助项目(2014ZX10002002-002)；

详细信息

中图分类号: R512.62
计量
- 文章访问数: 2037
- HTML全文浏览量: 21
- PDF下载量: 388
- 被引次数: 0
出版历程
- 收稿日期: 2016-06-07
- 出版日期: 2016-08-20

Regulatory effect of interleukin-10 on natural killer cells in patients with chronic hepatitis B

Hepatopathy Laboratory,The Third Affiliated Hospital of Sun Yat-sen University

Research funding:

摘要

摘要: 目前治疗手段难以彻底治愈慢性乙型肝炎（CHB）。自然杀伤细胞（NK细胞）是天然免疫的一个重要组成部分,在机体免疫监视和早期抗感染免疫过程中起重要作用。白细胞介素10（IL-10）是一种多功能负性调节因子,参与免疫细胞和炎症细胞等的生物调节。介绍了IL-10和NK细胞的特点及功能,CHB与IL-10和NK细胞的关系,以及IL-10和NK细胞在CHB治疗中的意义,认为在CHB中IL-10可能发挥了负性调控NK细胞功能的作用,但是能否通过阻断IL-10对NK细胞的调控作用提高NK细胞的抗病毒功能,同时避免NK细胞激活造成的肝脏免疫病理,仍有待进一步研究。
- 肝炎,乙型,慢性 /
- 白细胞介素10 /
- 杀伤细胞,天然 /
- 综述
Abstract: At present,it is very difficult to cure chronic hepatitis B( CHB) with current therapeutic methods. Natural killer( NK) cells are an important part of innate immunity and play an important role in immune surveillance and early anti- infectious immune process. Interleukin- 10( IL- 10) is a multifunctional negative regulatory factor and is involved in the biological regulation of immune cells and inflammatory cells. This article introduces the features and functions of IL- 10 and NK cells,the association of CHB with IL- 10 and NK cells,and the value of IL- 10 and NK cells in the treatment of CHB,and points out that in CHB,IL- 10 exerts a negative regulatory effect on NK cells. Further investigations are needed to confirm whether the antiviral function of NK cells can be enhanced through blocking the regulatory effect of IL- 10 on NK cells,and whether liver immunopathology induced by activation of NK cells can be avoided at the same time.
- hepatitis B /
- chronic /
- interleukin-10 /
- killer cells

HTML全文

参考文献(34)

[1]REHERMANN B,BERTOLETTI A.Immunological aspects of antiviral therapy of chronic hepatitis B virus and hepatitis C virus infections[J].Hepatology,2015,61(2):712-721.

[2]ASADULLAH K,STERRY W,VOLK HD.Interleukin-10 therapyreview of a new approach[J].Pharmacol Rev,2003,55(2):241-269.

[3]NI G,WANG T,WALTON S,et al.Manipulating IL-10 signalling blockade for better immunotherapy[J].Cell Immunol,2015,293(2):126-129.

[4]SARAIVA M,O'GARRA A.The regulation of IL-10 production by immune cells[J].Nate Rev Immunol,2010,10(3):170-181.

[5]NG CT,OLDSTONE MB.IL-10:achieving balance during persistent viral infection[J].Curr Top Microbiol Immunol,2014,380:129-144.

[6]GABRYSOVA L,HOWES A,SARAIVA M,et al.The regulation of IL-10 expression[J].Curr Top Microbiol Immunol,2014,380:157-190.

[7]D'ANDREA A,ASTE-AMEZAGA M,VALIANTE NM,et al.Interleukin 10(IL-10)inhibits human lymphocyte interferon gamma-production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells[J].J Exp Med,1993,178(3):1041-1048.

[8]MANNINO MH,ZHU Z,XIAO H,et al.The paradoxical role of IL-10 in immunity and cancer[J].Cancer Lett,2015,367(2):103-107.

[9]SAXENA A,KHOSRAVIANI S,NOEL S,et al.Interleukin-10paradox:a potent immunoregulatory cytokine that has been difficult to harness for immunotherapy[J].Cytokine,2015,74(1):27-34.

[10]LUNEMANN S,MALONE DF,HENGST J,et al.Compromised function of natural killer cells in acute and chronic viral hepatitis[J].J Infect Dis,2014,209(9):1362-1373.

[11]MAINI MK,PEPPA D.NK cells:a double-edged sword in chronic hepatitis B virus infection[J].Front Immunol,2013,4:57.

[12]WU SF,WANG WJ,GAO YQ.Natural killer cells in hepatitis Bvirus infection[J].Braz J Infect Dis,2015,19(4):417-425.

[13]BRYCESON YT,CHIANG SC,DARMANIN S,et al.Molecular mechanisms of natural killer cell activation[J].J Innate Immun,2011,3(3):216-226.

[14]PROTZER U,MAINI MK,KNOLLE PA.Living in the liver:hepatic infections[J].Nat Rev Immunol,2012,12(3):201-213.

[15]LANG PA,LANG KS,XU HC,et al.Natural killer cell activation enhances immune pathology and promotes chronic infection by limiting CD8+T-cell immunity[J].Proc Natl Acad Sci U S A,2012,109(4):1210-1215.

[16]JI HW.Effect of NK cells in the hepatitis B virus infection[J].China Med Herald,2014,11(34):161-165.(in Chinese)姬恒伟.NK细胞在乙型肝炎病毒感染中作用[J].中国医药导报,2014,11(34):161-165.

[17]DUNN C,PEPPA D,KHANNA P,et al.Temporal analysis of early immune responses in patients with acute hepatitis B virus infection[J].Gastroenterology,2009,137(4):1289-1300.

[18]PEPPA D,MICCO L,JAVAID A,et al.Blockade of immunosuppressive cytokines restores NK cell antiviral function in chronic hepatitis B virus infection[J].PLoS Pathog,2010,6(12):e1001227.

[19]HYODO N,NAKAMURA I,IMAWARI M.Hepatitis B core antigen stimulates interleukin-10 secretion by both T cells and monocytes from peripheral blood of patients with chronic hepatitis B virus infection[J].Clin Exp Immunol,2004,135(3):462-466.

[20]SU R,XIONG YL,LIU Y,et al.Characteristics of regulatory Bcells and serum IL-10,IP-10 in different immune phases of chronic hepatitis B virus infection[J/CD].Chin J Exp Clin Infect Dis:Electronic Edition,2015,9(4):468-473.(in Chinese)苏然,熊亚莉,刘勇,等.不同免疫状态下慢性HBV感染者外周血调节性B细胞及血清IL-10和IP-10的表达特点[J/CD].中华实验和临床感染病杂志:电子版,2015,9(4):468-473.

[21]DAS A,ELLIS G,PALLANT C,et al.IL-10-producing regulatory B cells in the pathogenesis of chronic hepatitis B virus infection[J].J Immunol,2012,189(8):3925-3935.

[22]WEBSTER G J,REIGNAT S,MAINI MK,et al.Incubation phase of acute hepatitis B in man:dynamic of cellular immune mechanisms[J].Hepatology,2000,32(5):1117-1124.

[23]FISICARO P,VALDATTA C,BONI C,et al.Early kinetics of innate and adaptive immune responses during hepatitis B virus infection[J].Gut,2009,58(7):974-982.

[24]JU Y,HOU N,MENG J,et al.T cell immunoglobulin-and mucin-domain-containing molecule-3(Tim-3)mediates natural killer cell suppression in chronic hepatitis B[J].J Hepatol,2010,52(3):322-329.

[25]ZHANG Z,ZHANG S,ZOU Z,et al.Hypercytolytic activity of hepatic natural killer cells correlates with liver injury in chronic hepatitis B patients[J].Hepatology,2011,53(1):73-85.

[26]TJWA ET,van OORD GW,HEGMANS JP,et al.Viral load reduction improves activation and function of natural killer cells in patients with chronic hepatitis B[J].J Hepatol,2011,54(2):209-218.

[27]TU Z,BOZORGZADEH A,PIERCE RH,et al.TLR-dependent cross talk between human Kupffer cells and NK cells[J].J Exp Med,2008,205(1):233-244.

[28]LASSEN MG,LUKENS JR,DOLINA JS,et al.Intrahepatic IL-10 maintains NKG2A+Ly49-liver NK cells in a functionally hyporesponsive state[J].J Immunol,2010,184(5):2693-2701.

[29]KAKIMI K,GUIDOTTI LG,KOEZUKA Y,et al.Natural killer Tcell activation inhibits hepatitis B virus replication in vivo[J].JExp Med,2000,192(7):921-930.

[30]GUIDOTTI LG,ROCHFORD R,CHUNG J,et al.Viral clearance without destruction of infected cells during acute HBV infection[J].Science,1999,284(5415):825-829.

[31]TREPO C,CHAN HL,LOK A.Hepatitis B virus infection[J].Lancet,2014,384(9959):2053-2063.

[32]MICCO L,PEPPA D,LOGGI E,et al.Differential boosting of innate and adaptive antiviral responses during pegylated-interferonalpha therapy of chronic hepatitis B[J].J Hepatol,2013,58(2):225-233.

[33]MAHDAVI M,AMIRRASOULI H,ALAVIAN SM,et al.Impact of pegylated interferon-alfa-2a on perforin level in patients with chronic hepatitis B;preliminary study[J].Hepat Mon,2013,13(11):e11903.

[34]MAINI MK,GEHRING AJ.The role of innate immunity in the immunopathology and treatment of HBV infection[J].J Hepatol,2016,64(1 Suppl):s60-s70.

施引文献

资源附件(0)

访问统计