白细胞介素-10

(重定向自白细胞介素10

白细胞介素-10(亦稱為介白素-10,英文:Interleukin 10,簡稱IL-10),也称为细胞激素合成抑制因子(cytokine synthesis inhibitory factor,CSIF),是一种抗炎症细胞因子。在人类中,IL-10由「IL10」基因编码。[6]IL-10的訊號需要藉由細胞膜上的介白素-10受體(IL-10受體)傳遞到細胞內。IL-10受體在作用時構型為含四個次單元的蛋白質複合體,其中包含兩個IL-10受體1(IL-10R1)單元以及兩個IL-10受體2(IL-10R2)單元。在接收到IL-10訊號時,IL-10R1會先直接與IL-10結合,之後呼叫(recruit)IL-10R2形成完整複合體,以進行後續的訊號傳遞,IL-10R2並不直接與IL-10結合。[7]IL-10通过JAK1和Tyk2分别磷酸化IL-10受体1、IL-10受体2的胞质尾端,来诱导STAT3信号传递。

白细胞介素-10
已知的結構
PDB直系同源搜索: PDBe RCSB
識別號
别名IL10;, CSIF, GVHDS, IL-10, IL10A, TGIF, interleukin 10
外部IDOMIM124092 MGI96537 HomoloGene478 GeneCardsIL10
相關疾病
貝賽特氏症、​溃疡性结肠炎[1]
基因位置(人类
1號染色體
染色体1號染色體[2]
1號染色體
白细胞介素-10的基因位置
白细胞介素-10的基因位置
基因座1q32.1起始206,767,602 bp[2]
终止206,774,541 bp[2]
RNA表达模式
查阅更多表达数据
直系同源
物種人類小鼠
Entrez
Ensembl
UniProt
mRNA​序列

NM_000572

NM_010548

蛋白序列

NP_000563

NP_034678

基因位置​(UCSC)Chr 1: 206.77 – 206.77 MbChr 1: 130.95 – 130.95 Mb
PubMed​查找[4][5]
維基數據
檢視/編輯人類檢視/編輯小鼠

基因和蛋白质结构

IL-10蛋白是同型二聚体,每个亚基的长度均为178个氨基酸[8]

IL-10被归为2类细胞因子——包括IL-19、IL-20、IL-22、IL-24(Mda-7)、IL-26和I型干扰素(IFN-α,-β,-ε,-κ,-ω),II型(IFN-γ),III型(IFN-λ,[9]也称为IL-28A,IL-28B,和IL-29)。[10]

表达与合成

在人类中,IL-10由「IL10」基因编码,该基因位于1号染色体上,包含5个外显子[6],主要由单核细胞产生,并在较小程度上由淋巴细胞产生,即II型T辅助细胞(TH2),肥大细胞,CD4+CD25+Foxp3+调节性T细胞,以及活化的T细胞B细胞的某些子集。在这些细胞中触发PD-1后,单核细胞可以产生IL-10[11]。IL-10上调也由GPCR介导,例如β-2肾上腺素[12]和2型大麻素[13]受体。IL-10的表达在未经刺激的组织中极少,似乎需要由共生或病原菌触发。[14]IL-10表达在转录和转录后水平受到严格调节。刺激TLR或Fc受体途径后,在单核细胞中观察到广泛的IL-10基因座重塑[15]。IL-10诱导涉及ERK1/2,p38和NF-κB信号传导,以及通过转录因子NF-κB和AP-1的启动子结合而引起的转录激活。IL-10可能通过负反馈回路自动调节其表达,该回路涉及IL-10受体的自分泌刺激和p38信号通路的抑制[16]。此外,IL-10的表达在转录后水平受到广泛调控,这可能涉及通过富含AU的元件[17]和诸如let-7[18]或miR-106的microRNA控制mRNA的稳定性[19]

功能

IL-10是一种在免疫调节和炎症中具有多效性的细胞因子。它下调了巨噬细胞上Th1细胞因子、MHC-II类抗原、共刺激分子的表达。它还增强了B细胞的生存、增殖和产生抗体的能力。IL-10可以阻断NF-kB活动,并参与JAK-STAT信号转导通路的调节。

IL-10发现与1991年[20],最初报道其抑制细胞分泌、抗原呈递和CD4+细胞活化。[21][22][23][24]进一步的研究表明,IL-10主要抑制脂多糖(LPS)和细菌产物介导的促炎性细胞因子TNFα[25]、IL-1β[25]、IL-12[26]、IFNγ[27]的分泌,这些细胞因子由Toll样受体(TLR)触发的骨髓细胞谱系分泌。

对肿瘤的影响

随着时间的流逝,IL-10功能的细微差别出现了,因为已证明对荷瘤小鼠的治疗可抑制肿瘤转移[28]。多个实验室的进一步研究已经产生了进一步支持IL-10在免疫神经学背景下的免疫刺激能力的数据。从IL-10转基因小鼠[29]中转染的肿瘤细胞系[30][31]中表达IL-10或用IL-10给药可控制原发性肿瘤生长并降低转移负担。[32][33]最近,聚乙二醇化重组鼠IL-10(PEG-rMuIL-10)已显示出诱导IFNγ和CD8+T细胞依赖性抗肿瘤免疫力[34][35]。更具体地,已显示PEG化的重组人IL-10(PEG-rHuIL-10)增强细胞毒性分子粒酶B和穿孔素的CD8+T细胞分泌,并增强T细胞受体依赖性IFNγ的分泌[36]

在疾病中的作用

对小鼠的研究表明,肥大细胞也产生IL-10,抵消了这些细胞在变态反应部位的炎症作用[37]

IL-10能够抑制由巨噬细胞和Th1T细胞等细胞产生的促炎细胞因子如IFN-γIL-2IL-3TNFαGM-CSF的合成。它也显示出抑制抗原呈递细胞的抗原呈递能力的强大能力。但是,它也对某些T细胞(Th2)和肥大细胞具有刺激性,并刺激B细胞成熟和抗体产生。

IL-10检查环氧合酶Cyclo-oxygenase-2(COX-2)的可诱导形式。缺乏IL-10已被证明可导致COX激活并导致血栓烷受体激活,从而引起小鼠血管内皮和心脏功能障碍。白介素10基因敲除脆弱的小鼠会随着年龄的增长而出现心脏和血管功能障碍[38]

IL-10与肌动蛋白有关,因为运动会引起IL-1ra,IL-10和sTNF-R的循环水平增加,这表明体育锻炼可促进抗炎细胞因子的形成。[39][40]

与健康个体相比,在诊断为多发性硬化症的个体中观察到较低水平的IL-10[41]。由于IL-10水平的降低,TNFα水平不能得到有效调节,因为IL-10可以调节TNF-α转化酶[42]。结果,TNFα水平升高并导致炎症。[43]TNFα本身通过TNF受体1诱导少突胶质细胞脱髓鞘,而慢性炎症与神经元脱髓鞘有关。

黑素瘤细胞系中,IL-10调节NKG2D配体的表面表达。[44]

临床使用或试验

在小鼠中进行的基因敲除研究表明,这种细胞因子在肠道中是必需的免疫调节剂。[45]的确,克罗恩氏病患者对用重组白介素10产生细菌的治疗反应良好,证明了IL-10对抵消人体过度活跃的免疫反应的重要性。[46]

根据数据,在临床试验中,数千名患有各种自身免疫性疾病的患者接受了重组人IL-10(rHuIL-10)的治疗。与预期相反,rHuIL-10治疗并未对克罗恩病患者的疾病产生重大影响。[47][48][49]或类风湿关节炎。[50]rHuIL-10治疗最初在牛皮癣中显示出有希望的临床数据。[51]但在一项随机,双盲,安慰剂对照的II期临床试验中未能达到临床意义。[52]对rHuIL-10在人类中作用的进一步研究表明,rHuIL-10除了抑制炎症外,还能够发挥促炎作用。[53][54]

聚乙二醇化形式

除这些数据外,目前正在进行一项I期免疫科学临床试验,以评估PEG化重组人IL-10(PEG-rHuIL-10,AM0010)的治疗能力。[55]与临床前免疫免疫学数据一致,研究者报告了实质性的抗肿瘤功效。相反于所报告的在体外和体内产生的IL-10的免疫抑制作用,[22][23][24][56][57]治疗癌症患者的PEG-重组人白介-10引发的剂量滴定感应的免疫刺激细胞因子IFNγ,IL-18,IL-7,GM-CSF和IL-4的表达。此外,接受治疗的患者的外周CD8+T细胞表达活化标记,例如程序性死亡配體1(PD-L1)+,淋巴细胞活化基因3(LAG3)+和Fas配体(FasL)升高,血清TGFβ降低,其折叠倍数增加。这些发现与使用PEG-rMuIL-10的已发表的临床前免疫科学报告[34][35]以及以前用rHuIL-10治疗人类的发现一致。[53][54]这些数据表明,尽管IL-10可以在细菌产物刺激的髓样细胞中发挥免疫抑制作用,但对人的rHuIL-10/PEG-rHuIL-10治疗主要是免疫刺激。截至2018年 (2018-Missing required parameter 1=month!)AM0010(又名pegilodecakin)正在进行3期临床试验。[58]

互动

已经证明IL-10与白介素10受体α亚基相互作用[59][60][61][62][63]

IL-10受体复合物也需要IL10R2链来启动信号传导。这种配体-受体的组合存在于鸟类和青蛙中,也可能存在于骨鱼类中。 

参考资料


  1. ^ 與白细胞介素-10相關的疾病;在維基數據上查看/編輯參考. 
  2. ^ 2.0 2.1 2.2 GRCh38: Ensembl release 89: ENSG00000136634 - Ensembl, May 2017
  3. ^ 3.0 3.1 3.2 GRCm38: Ensembl release 89: ENSMUSG00000016529 - Ensembl, May 2017
  4. ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
  5. ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
  6. ^ 6.0 6.1 Mapping of the human IL10 gene and further characterization of the 5' flanking sequence. Immunogenetics. 1997, 46 (2): 120–8. PMID 9162098. doi:10.1007/s002510050250. 
  7. ^ Interleukin-10: new perspectives on an old cytokine. Immunological Reviews. December 2008, 226 (1): 205–18. PMC 2724982 . PMID 19161426. doi:10.1111/j.1600-065X.2008.00706.x. 
  8. ^ Crystal structure of interleukin-10 reveals the functional dimer with an unexpected topological similarity to interferon gamma. Structure. June 1995, 3 (6): 591–601. PMID 8590020. doi:10.1016/S0969-2126(01)00193-9. 
  9. ^ Interferon-λ: Immune Functions at Barrier Surfaces and Beyond. Immunity. July 2015, 43 (1): 15–28. PMC 4527169 . PMID 26200010. doi:10.1016/j.immuni.2015.07.001. 
  10. ^ Interleukin-10 and related cytokines and receptors. Annual Review of Immunology. 2004, 22 (1): 929–79. PMID 15032600. doi:10.1146/annurev.immunol.22.012703.104622. 
  11. ^ Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection. Nature Medicine. April 2010, 16 (4): 452–9. PMC 4229134 . PMID 20208540. doi:10.1038/nm.2106. 
  12. ^ Ağaç, Didem; Estrada, Leonardo D.; Maples, Robert; Hooper, Lora V.; Farrar, J. David. The β2-adrenergic receptor controls inflammation by driving rapid IL-10 secretion. Brain, Behavior, and Immunity. November 2018, 74: 176–185. ISSN 1090-2139. PMC 6289674 . PMID 30195028. doi:10.1016/j.bbi.2018.09.004. 
  13. ^ Saroz, Yurii; Kho, Dan T.; Glass, Michelle; Graham, Euan Scott; Grimsey, Natasha Lillia. Cannabinoid Receptor 2 (CB 2 ) Signals via G-alpha-s and Induces IL-6 and IL-10 Cytokine Secretion in Human Primary Leukocytes. ACS Pharmacology & Translational Science. 2019-10-19, 2 (6): 414–428. ISSN 2575-9108. doi:10.1021/acsptsci.9b00049 (英语). 
  14. ^ IL-35 is a novel responsive anti-inflammatory cytokine--a new system of categorizing anti-inflammatory cytokines. PLOS ONE. March 2012, 7 (3): e33628. PMC 3306427 . PMID 22438968. doi:10.1371/journal.pone.0033628. 
  15. ^ The regulation of IL-10 production by immune cells. Nature Reviews. Immunology. March 2010, 10 (3): 170–81. PMID 20154735. doi:10.1038/nri2711. 
  16. ^ Control of dual-specificity phosphatase-1 expression in activated macrophages by IL-10. European Journal of Immunology. October 2005, 35 (10): 2991–3001. PMID 16184516. doi:10.1002/eji.200526192. 
  17. ^ Posttranscriptional regulation of IL-10 gene expression through sequences in the 3'-untranslated region. Journal of Immunology. July 2000, 165 (1): 292–6. PMID 10861064. doi:10.4049/jimmunol.165.1.292. 
  18. ^ Analysis of the host microRNA response to Salmonella uncovers the control of major cytokines by the let-7 family. The EMBO Journal. May 2011, 30 (10): 1977–89. PMC 3098495 . PMID 21468030. doi:10.1038/emboj.2011.94. 
  19. ^ Posttranscriptional regulation of interleukin-10 expression by hsa-miR-106a. Proceedings of the National Academy of Sciences of the United States of America. April 2009, 106 (14): 5761–6. PMC 2659714 . PMID 19307576. doi:10.1073/pnas.0808743106. 
  20. ^ Interleukin-10 and the interleukin-10 receptor. Annual Review of Immunology. 2001-01-01, 19 (1): 683–765. PMID 11244051. doi:10.1146/annurev.immunol.19.1.683. 
  21. ^ Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. The Journal of Experimental Medicine. November 1991, 174 (5): 1209–20. PMC 2119001 . PMID 1940799. doi:10.1084/jem.174.5.1209. 
  22. ^ 22.0 22.1 Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. The Journal of Experimental Medicine. October 1991, 174 (4): 915–24. PMC 2118975 . PMID 1655948. doi:10.1084/jem.174.4.915. 
  23. ^ 23.0 23.1 A molecular basis for T cell suppression by IL-10: CD28-associated IL-10 receptor inhibits CD28 tyrosine phosphorylation and phosphatidylinositol 3-kinase binding. FASEB Journal. September 2000, 14 (12): 1666–8. PMID 10973911. doi:10.1096/fj.99-0874fje. 
  24. ^ 24.0 24.1 IL-10 directly acts on T cells by specifically altering the CD28 co-stimulation pathway. European Journal of Immunology. June 2000, 30 (6): 1683–90. PMID 10898505. doi:10.1002/1521-4141(200006)30:6<1683::AID-IMMU1683>3.0.CO;2-A. 
  25. ^ 25.0 25.1 Opp MR, Smith EM, Hughes TK. Interleukin-10 (cytokine synthesis inhibitory factor) acts in the central nervous system of rats to reduce sleep. Journal of Neuroimmunology. July 1995, 60 (1–2): 165–8. PMID 7642744. doi:10.1016/0165-5728(95)00066-b. 
  26. ^ Aste-Amezaga M, Ma X, Sartori A, Trinchieri G. Molecular mechanisms of the induction of IL-12 and its inhibition by IL-10. Journal of Immunology. June 1998, 160 (12): 5936–44. PMID 9637507. 
  27. ^ Varma TK, Toliver-Kinsky TE, Lin CY, Koutrouvelis AP, Nichols JE, Sherwood ER. Cellular mechanisms that cause suppressed gamma interferon secretion in endotoxin-tolerant mice. Infection and Immunity. September 2001, 69 (9): 5249–63. PMC 98633 . PMID 11500393. doi:10.1128/iai.69.9.5249-5263.2001. 
  28. ^ Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanism. The Journal of Experimental Medicine. August 1996, 184 (2): 579–84. PMC 2192723 . PMID 8760811. doi:10.1084/jem.184.2.579. 
  29. ^ A transgenic model to analyze the immunoregulatory role of IL-10 secreted by antigen-presenting cells. Journal of Immunology. February 1999, 162 (3): 1723–9. PMID 9973435. 
  30. ^ Interleukin-10 gene transfer activates interferon-gamma and the interferon-gamma-inducible genes Gbp-1/Mag-1 and Mig-1 in mammary tumors. International Journal of Cancer. February 1999, 80 (4): 624–9. PMID 9935167. doi:10.1002/(sici)1097-0215(19990209)80:4<624::aid-ijc23>3.0.co;2-9. 
  31. ^ Essential role of nitric oxide and interferon-gamma for tumor immunotherapy with interleukin-10. Journal of Immunotherapy. 2000-04-01, 23 (2): 208–14. PMID 10746547. doi:10.1097/00002371-200003000-00005. 
  32. ^ Interleukin-10 promotes the maintenance of antitumor CD8(+) T-cell effector function in situ. Blood. October 2001, 98 (7): 2143–51. PMID 11568001. doi:10.1182/blood.v98.7.2143. 
  33. ^ Systemic administration of cellular IL-10 induces an effective, specific, and long-lived immune response against established tumors in mice. Journal of Immunology. July 1996, 157 (1): 231–8. PMID 8683120. 
  34. ^ 34.0 34.1 IL-10 directly activates and expands tumor-resident CD8(+) T cells without de novo infiltration from secondary lymphoid organs. Cancer Research. July 2012, 72 (14): 3570–81. PMID 22581824. doi:10.1158/0008-5472.CAN-12-0721. 
  35. ^ 35.0 35.1 IL-10 elicits IFNγ-dependent tumor immune surveillance. Cancer Cell. December 2011, 20 (6): 781–96. PMID 22172723. doi:10.1016/j.ccr.2011.11.003. 
  36. ^ The Potentiation of IFN-γ and Induction of Cytotoxic Proteins by Pegylated IL-10 in Human CD8 T Cells. Journal of Interferon & Cytokine Research. December 2015, 35 (12): 948–55. PMID 26309093. doi:10.1089/jir.2014.0221. 
  37. ^ Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B. Nature Immunology. October 2007, 8 (10): 1095–104. PMID 17767162. doi:10.1038/ni1503. 
  38. ^ Interleukin 10 knockout frail mice develop cardiac and vascular dysfunction with increased age. Experimental Gerontology. February 2013, 48 (2): 128–35. PMC 3744178 . PMID 23159957. doi:10.1016/j.exger.2012.11.001. 
  39. ^ Physical activity and plasma interleukin-6 in humans--effect of intensity of exercise. European Journal of Applied Physiology. December 2000, 83 (6): 512–5. PMID 11192058. doi:10.1007/s004210000312. 
  40. ^ Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans. The Journal of Physiology. February 1999, 515 (1): 287–91. PMC 2269132 . PMID 9925898. doi:10.1111/j.1469-7793.1999.287ad.x. 
  41. ^ Multiple sclerosis: levels of interleukin-10-secreting blood mononuclear cells are low in untreated patients but augmented during interferon-beta-1b treatment. Scandinavian Journal of Immunology. May 1999, 49 (5): 554–61. PMID 10320650. doi:10.1046/j.1365-3083.1999.00546.x. 
  42. ^ Interleukin-10 regulates TNF-alpha-converting enzyme (TACE/ADAM-17) involving a TIMP-3 dependent and independent mechanism. European Journal of Immunology. April 2008, 38 (4): 1106–17. PMID 18383040. doi:10.1002/eji.200737821. 
  43. ^ Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy. Clinical Reviews in Allergy & Immunology. February 2012, 42 (1): 26–34. PMID 22189514. doi:10.1007/s12016-011-8287-6. 
  44. ^ Interleukin 10 decreases MICA expression on melanoma cell surface. Immunology and Cell Biology. March 2011, 89 (3): 447–57. PMID 20714339. doi:10.1038/icb.2010.100. 
  45. ^ Entrez Gene: IL10 interleukin 10. 
  46. ^ A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease. Clinical Gastroenterology and Hepatology. June 2006, 4 (6): 754–9. PMID 16716759. doi:10.1016/j.cgh.2006.03.028. 
  47. ^ Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn's disease. The Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group. Gastroenterology. December 2000, 119 (6): 1473–82. PMID 11113068. doi:10.1053/gast.2000.20229. 
  48. ^ Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease. Crohn's Disease IL-10 Cooperative Study Group. Gastroenterology. December 2000, 119 (6): 1461–72. PMID 11113067. doi:10.1053/gast.2000.20196. 
  49. ^ Multiple doses of intravenous interleukin 10 in steroid-refractory Crohn's disease. Crohn's Disease Study Group. Gastroenterology. August 1997, 113 (2): 383–9. PMID 9247454. doi:10.1053/gast.1997.v113.pm9247454. 
  50. ^ Interleukin 10 treatment of patients with rheumatoid arthritis enhances Fc gamma receptor expression on monocytes and responsiveness to immune complex stimulation. The Journal of Rheumatology. April 2003, 30 (4): 648–51. PMID 12672180. 
  51. ^ Interleukin 10 treatment of psoriasis: clinical results of a phase 2 trial. Archives of Dermatology. February 1999, 135 (2): 187–92. PMID 10052405. doi:10.1001/archderm.135.2.187. 
  52. ^ Clinical and immunologic assessment of patients with psoriasis in a randomized, double-blind, placebo-controlled trial using recombinant human interleukin 10. Archives of Dermatology. October 2002, 138 (10): 1341–6. PMID 12374540. doi:10.1001/archderm.138.10.1341. 
  53. ^ 53.0 53.1 Proinflammatory effects of IL-10 during human endotoxemia. Journal of Immunology. September 2000, 165 (5): 2783–9. PMID 10946310. doi:10.4049/jimmunol.165.5.2783. 
  54. ^ 54.0 54.1 Treatment of Crohn's disease with recombinant human interleukin 10 induces the proinflammatory cytokine interferon gamma. Gut. February 2002, 50 (2): 191–5. PMC 1773093 . PMID 11788558. doi:10.1136/gut.50.2.191. 
  55. ^ Infante, Jeffrey R.; Naing, Aung; Papadopoulos, Kyriakos P.; Autio, Karen A.; Ott, Patrick Alexander; Wong, Deborah Jean Lee; Falchook, Gerald Steven; Patel, Manish R.; Pant, Shubham. A first-in-human dose escalation study of PEGylated recombinant human IL-10 (AM0010) in advanced solid tumors.. ASCO Meeting Abstracts. 2015-05-20, 33 (15_suppl): 3017 [2020-03-03]. (原始内容 (vanc)存档于2015-12-22). 
  56. ^ Interleukin-10 (cytokine synthesis inhibitory factor) acts in the central nervous system of rats to reduce sleep. Journal of Neuroimmunology. July 1995, 60 (1–2): 165–8. PMID 7642744. doi:10.1016/0165-5728(95)00066-b. 
  57. ^ Molecular mechanisms of the induction of IL-12 and its inhibition by IL-10. Journal of Immunology. June 1998, 160 (12): 5936–44. PMID 9637507. 
  58. ^ Early Data Supports Phase 3 Trial of Pegilodecakin as Possible Treatment for Advanced Pancreatic Cancer. [2020-03-03]. (原始内容存档于2021-12-02). 
  59. ^ A receptor for interleukin 10 is related to interferon receptors. Proceedings of the National Academy of Sciences of the United States of America. December 1993, 90 (23): 11267–71. PMC 47963 . PMID 8248239. doi:10.1073/pnas.90.23.11267. 
  60. ^ Crystal structure of the IL-10/IL-10R1 complex reveals a shared receptor binding site. Immunity. July 2001, 15 (1): 35–46. PMID 11485736. doi:10.1016/S1074-7613(01)00169-8. 
  61. ^ Characterization of recombinant extracellular domain of human interleukin-10 receptor. The Journal of Biological Chemistry. May 1995, 270 (21): 12906–11. PMID 7759550. doi:10.1074/jbc.270.21.12906. 
  62. ^ Purification, crystallization and preliminary X-ray diffraction of a complex between IL-10 and soluble IL-10R1. Acta Crystallographica Section D. December 2001, 57 (Pt 12): 1908–11. PMID 11717514. doi:10.1107/S0907444901016249. 
  63. ^ Purification of receptor complexes of interleukin-10 stoichiometry and the importance of deglycosylation in their crystallization. European Journal of Biochemistry. May 1999, 262 (1): 134–41. PMID 10231374. doi:10.1046/j.1432-1327.1999.00363.x. 

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