白介素-2治疗自身免疫性肝炎疗效研究进展与展望*

doi:10.3969/j.issn.1672-5069.2025.03.003

摘要/Abstract

关键词: 自身免疫性肝炎, 白介素-2, 调节性T细胞, 效应性T细胞, 治疗

Key words: Autoimmune hepatitis, Interleukin-2, Regulatory T cells, Effector T cells, Therapy

罗悦心, 罗红春. 白介素-2治疗自身免疫性肝炎疗效研究进展与展望^*[J]. 实用肝脏病杂志, 2025, 28(3): 330-333.

Luo Yuexin, Luo Hongchun. Interleukin-2 in the treatment of patients with autoimmune hepatitis: current state of the art, controversies, and perspectives[J]. Journal of Practical Hepatology, 2025, 28(3): 330-333.

参考文献

[1] 中华医学会肝病学分会. 自身免疫性肝炎诊断和治疗指南(2021年). 临床肝胆病杂志, 2022, 38(1): 42-49.
[2] Taubert R, Hardtke-Wolenski M, Noyan F, et al. Intrahepatic regulatory T cells in autoimmune hepatitis are associated with treatment response and depleted with current therapies. J Hepatol,2014, 61(5): 1106-1114.
[3] Malek TR. The biology of interleukin-2. Annu Rev Immunol, 2008, 26: 453-479.
[4] Denny P, Lord CJ, Hill NJ, et al. Mapping of the IDDM locus Idd3 to a 0.35-cM interval containing the interleukin-2 gene. Diabetes, 1997, 46(4): 695-700.
[5] Kane LP, Lin J, Weiss A. It's all relative: NF-kappaB and CD28 costimulation of T-cell activation. Trends Immunol, 2002, 23(8): 413-420.
[6] Isakov N, Altman A. Protein kinase C(theta) in T cell activation. Annu Rev Immunol, 2002, 20: 761-794.
[7] Ho IC, Kim JI, Szabo SJ, et al. Tissue-specific regulation of cytokine gene expression. Cold Spring Harb Symp Quant Biol, 1999, 64: 573-584.
[8] Rickert M, Wang X, Boulanger MJ, et al. The structure of interleukin-2 complexed with its alpha receptor. Science, 2005, 308(5727): 1477-1480.
[9] Takeshita T, Asao H, Ohtani K, et al. Cloning of the gamma chain of the human IL-2 receptor. Science, 1992, 257(5068): 379-382.
[10] Smith GA, Taunton J, Weiss A. IL-2Rβ abundance differentially tunes IL-2 signaling dynamics in CD4(+) and CD8(+) T cells. Sci Signal, 2017, 10(510).
[11] Wang X, Rickert M, Garcia KC. Structure of the quaternary complex of interleukin-2 with its alpha, beta, and gammac receptors. Science, 2005, 310(5751): 1159-1163.
[12] Fontenot JD, Rasmussen JP, Gavin MA, et al. A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat Immunol, 2005, 6(11): 1142-1151.
[13] Boyman O, Sprent J. The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol, 2012, 12(3): 180-190.
[14] Goudy K, Aydin D, Barzaghi F, et al. Human IL2RA null mutation mediates immunodeficiency with lymphoproliferation and autoimmunity. Clin Immunol, 2013, 146(3): 248-261.
[15] Sakaguchi S, Sakaguchi N, Asano M, et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol, 1995, 155(3): 1151-1164.
[16] Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science, 2003, 299(5609): 1057-1061.
[17] Miyara M, Gorochov G, Ehrenstein M, et al. Human FoxP3+ regulatory T cells in systemic autoimmune diseases. Autoimmun Rev, 2011, 10(12): 744-755.
[18] Longhi MS, Ma Y, Mitry RR, et al. Effect of CD4⁺ CD25⁺ regulatory T-cells on CD8 T-cell function in patients with autoimmune hepatitis. J Autoimmun, 2005, 25(1): 63-71.
[19] Longhi MS, Ma Y, Bogdanos DP, et al. Impairment of CD4(+)CD25(+) regulatory T-cells in autoimmune liver disease. J Hepatol, 2004, 41(1): 31-37.
[20] Dominguez-Villar M, Hafler DA. Regulatory T cells in autoimmune disease. Nat Immunol, 2018, 19(7): 665-673.
[21] Abbas AK, Trotta E, D RS, et al. Revisiting IL-2: Biology and therapeutic prospects. Sci Immunol, 2018, 3(25):1213-1217.
[22] Morgan DA, Ruscetti FW, Gallo R. Selective in vitro growth of T lymphocytes from normal human bone marrows. Science, 1976, 193(4257): 1007-1008.
[23] Miyazaki T, Liu ZJ, Kawahara A, et al. Three distinct IL-2 signaling pathways mediated by bcl-2, c-myc, and lck cooperate in hematopoietic cell proliferation. Cell, 1995, 81(2): 223-231.
[24] Josefowicz SZ, Lu LF, Rudensky AY. Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol, 2012, 30: 531-564.
[25] Busse D, de la Rosa M, Hobiger K, et al. Competing feedback loops shape IL-2 signaling between helper and regulatory T lymphocytes in cellular microenvironments. Proc Nat Acad Sci, 2010, 107(7): 3058-3063.
[26] Chinen T, Kannan AK, Levine AG, et al. An essential role for the IL-2 receptor in T(reg) cell function. Nat Immunol, 2016, 17(11): 1322-1333.
[27] Barron L, Dooms H, Hoyer KK, et al. Cutting edge: mechanisms of IL-2-dependent maintenance of functional regulatory T cells. J Immunol, 2010, 185(11): 6426-6430.
[28] Leonard WJ, Lin JX. Strategies to therapeutically modulate cytokine action. Nat Rev Drug Discov, 2023, 22(10): 827-854.
[29] Saadoun D, Rosenzwajg M, Joly F, et al. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med, 2011, 365(22): 2067-2077.
[30] Yu A, Snowhite I, Vendrame F, et al. Selective IL-2 responsiveness of regulatory T cells through multiple intrinsic mechanisms supports the use of low-dose IL-2 therapy in type 1 diabetes. Diabetes, 2015, 64(6): 2172-2183.
[31] Rosenzwajg M, Lorenzon R, Cacoub P, et al. Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial. Ann Rheum Dis, 2019, 78(2): 209-217.
[32] Kim S, Maeng JY, Hyun SJ, et al. Extracellular vesicles from human umbilical cord blood plasma modulate interleukin-2 signaling of T cells to ameliorate experimental autoimmune encephalomyelitis. Theranostics, 2020, 10(11): 5011-5028.
[33] Klatzmann D, Abbas AK. The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases. Nat Rev Immunol, 2015, 15(5): 283-294.
[34] Arenas-Ramirez N, Woytschak J, Boyman O. Interleukin-2: Biology, design and application. Trends Immunol, 2015, 36(12): 763-777.
[35] Boyman O, Kovar M, Rubinstein MP, et al. Selective stimulation of T cell subsets with antibody-cytokine immune complexes. Science, 2006, 311(5769): 1924-1927.
[36] Buitrago-Molina LE, Pietrek J, Noyan F, et al. Treg-specific IL-2 therapy can reestablish intrahepatic immune regulation in autoimmune hepatitis. J Autoimmun, 2021, 117: 102591.
[37] Spangler JB, Tomala J, Luca VC, et al. Antibodies to interleukin-2 elicit selective T cell subset potentiation through distinct conformational mechanisms. Immunity, 2015, 42(5): 815-825.
[38] Trotta E, Bessette PH, Silveria SL, et al. A human anti-IL-2 antibody that potentiates regulatory T cells by a structure-based mechanism. Nat Med, 2018, 24(7): 1005-1014.
[39] Tchao N, Gorski KS, Yuraszeck T, et al. Amg 592 is an investigational IL-2 mutein that induces highly selective expansion of regulatory T cells. Blood, 2017, 130(Supplement 1): 696-696.
[40] Gorski KS, Stern J, Hsu Y-H, et al. THU0031 phenotype of foxp3⁺ regulatory T-cells expanded by the il-2 mutein, amg 592 in healthy subjects in phase 1, first-in-human study. Ann Rheumat Dis, 2018, 77(Suppl 2): 243-243.
[41] Peterson LB, Bell CJM, Howlett SK, et al. A long-lived IL-2 mutein that selectively activates and expands regulatory T cells as a therapy for autoimmune disease. J Autoimmun, 2018, 95: 1-14.
[42] Hsieh YT, Hubeau C, Massa V, et al. OP0316 emerging best-in-class IL-2 variant highlights TREG-directed therapy for autoimmune disease. Ann Rheumat Dis, 2020, 79(Suppl 1): 195-195.
[43] Khoryati L, Pham MN, Sherve M, et al. An IL-2 mutein engineered to promote expansion of regulatory T cells arrests ongoing autoimmunity in mice. Sci Immunol, 2020, 5(50):329-334.
[44] Zhang B, Sun J, Wang Y, et al. Site-specific PEGylation of interleukin-2 enhances immunosuppression via the sustained activation of regulatory T cells. Nat Biomed Eng, 2021, 5(11): 1288-1305.
[45] Ottolenghi A, Bolel P, Sarkar R, et al. Life-extended glycosylated IL-2 promotes Treg induction and suppression of autoimmunity. Sci Rep, 2021, 11(1): 7676.

白介素-2治疗自身免疫性肝炎疗效研究进展与展望^*

Interleukin-2 in the treatment of patients with autoimmune hepatitis: current state of the art, controversies, and perspectives

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	孔丽霞, 陈旭峰, 许艳, 周建飞, 孙舒. 恩替卡韦经治慢性乙型肝炎低病毒血症患者联合或序贯艾米替诺福韦治疗疗效研究^*[J]. 实用肝脏病杂志, 2025, 28(3): 334-337.
[2]	王浩, 王清园, 沈琼, 许宇文. 聚乙二醇化干扰素α-2a联合艾尔巴韦/格拉瑞韦治疗慢性丙型肝炎患者疗效研究^*[J]. 实用肝脏病杂志, 2025, 28(3): 346-349.
[3]	徐玲玲, 卢远, 郑燕钗, 杨本场. 二甲双胍联合双环醇治疗非酒精性脂肪性肝炎患者短期疗效研究^*[J]. 实用肝脏病杂志, 2025, 28(3): 358-361.
[4]	温大超, 张秋萍, 石凌. 穴位贴敷联合运动处方治疗非酒精性脂肪性肝病患者疗效初步研究^*[J]. 实用肝脏病杂志, 2025, 28(3): 370-373.
[5]	马丹彤, 杨爽, 高丽丽, 高学松, 段雪飞. 伴有自身免疫现象的药物性肝损伤患者临床特征分析^*[J]. 实用肝脏病杂志, 2025, 28(3): 390-393.
[6]	李勇飞, 许正锯, 叶巧霞, 威晋. 血浆置换联合血液滤过治疗慢加急性乙型肝炎肝衰竭患者疗效研究^*[J]. 实用肝脏病杂志, 2025, 28(3): 394-397.
[7]	许荣波, 王艳, 王晓松, 王晓燕. 内镜曲张静脉套扎术联合生长抑素和艾司奥美拉唑治疗肝硬化并发食管胃静脉曲张破裂出血患者疗效研究^*[J]. 实用肝脏病杂志, 2025, 28(3): 410-413.
[8]	蒋召芹, 宋洁, 穆永芳. 内镜曲张静脉套扎术联合生长抑素和奥美拉唑治疗肝硬化并发食管胃底静脉曲张破裂出血患者疗效研究^*[J]. 实用肝脏病杂志, 2025, 28(3): 422-425.
[9]	杨懿瑾, 洪晗, 陈彬, 崔洪全, 王逸, 张甲. FOLFOX肝动脉灌注化疗联合仑伐替尼和PD-1抑制剂治疗中晚期原发性肝癌患者疗效研究^*[J]. 实用肝脏病杂志, 2025, 28(3): 426-429.
[10]	刘松涛, 李娟, 刘梅, 刘晖, 闾军. 15例肝细胞癌发生消化道穿孔患者临床特征分析^*[J]. 实用肝脏病杂志, 2025, 28(3): 430-433.
[11]	李宏建, 许织文, 夏斐, 盛建国. 超声引导穿刺引流治疗细菌性肝脓肿患者疗效研究^*[J]. 实用肝脏病杂志, 2025, 28(3): 454-457.
[12]	晏化军, 陈兴云, 马兵, 杨冲. UG-PTGD联合LC术治疗急性结石梗阻性胆囊炎患者疗效研究^*[J]. 实用肝脏病杂志, 2025, 28(3): 458-461.
[13]	冯淞, 李连杰, 程波. PTGD序贯保留胆囊动脉主干的LC术治疗急性胆囊炎患者疗效研究^*[J]. 实用肝脏病杂志, 2025, 28(3): 462-465.
[14]	柯俊杰, 邢杰宇, 张明英. 内镜逆行胰胆管造影术与腹腔镜胆总管切开探查术治疗胆囊切除术后胆总管结石患者效果比较^*[J]. 实用肝脏病杂志, 2025, 28(3): 466-469.
[15]	吕天富, 南琼. 经颈静脉肝内门体分流术治疗肝硬化门静脉高压症患者抗凝治疗研究进展[J]. 实用肝脏病杂志, 2025, 28(2): 165-168.