跳至內容

白細胞介素-10

本頁使用了標題或全文手工轉換
維基百科,自由的百科全書
白細胞介素-10
已知的結構
PDB直系同源搜索: PDBe RCSB
識別號
別名IL10;, CSIF, GVHDS, IL-10, IL10A, TGIF, interleukin 10
外部IDOMIM124092 MGI96537 HomoloGene478 GeneCardsIL10
相關疾病
貝賽特氏症、​潰瘍性結腸炎[1]
基因位置(人類
1號染色體
染色體1號染色體[2]
1號染色體
白細胞介素-10的基因位置
白細胞介素-10的基因位置
基因座1q32.1起始206,767,602 bp[2]
終止206,774,541 bp[2]
RNA表達模式
查閱更多表達數據
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

白細胞介素-10(亦稱為介白素-10,英文:Interleukin 10,簡稱IL-10),也稱為細胞激素合成抑制因子(cytokine synthesis inhibitory factor,CSIF),是一種抗炎症細胞因子。在人類中,IL-10由「IL10」基因編碼。[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通過JAK1和Tyk2分別磷酸化IL-10受體1、IL-10受體2的胞質尾端,來誘導STAT3信號傳遞。

基因和蛋白質結構

IL-10蛋白是同型二聚體,每個亞基的長度均為178個氨基酸[8]

IL-10被歸為2類細胞因子——包括IL-19、IL-20、IL-22、IL-24(Mda-7)、IL-26和I型干擾素(IFN-α,-β,-ε,-κ,-ω),II型(IFN-γ),III型(IFN-λ,[9]也稱為IL-28A,IL-28B,和IL-29)。[10]

表達與合成

在人類中,IL-10由「IL10」基因編碼,該基因位於1號染色體上,包含5個外顯子[6],主要由單核細胞產生,並在較小程度上由淋巴細胞產生,即II型T輔助細胞(TH2),肥大細胞,CD4+CD25+Foxp3+調節性T細胞,以及活化的T細胞B細胞的某些子集。在這些細胞中觸發PD-1後,單核細胞可以產生IL-10[11]。IL-10上調也由GPCR介導,例如β-2腎上腺素[12]和2型大麻素[13]受體。IL-10的表達在未經刺激的組織中極少,似乎需要由共生或病原菌觸發。[14]IL-10表達在轉錄和轉錄後水平受到嚴格調節。刺激TLR或Fc受體途徑後,在單核細胞中觀察到廣泛的IL-10基因座重塑[15]。IL-10誘導涉及ERK1/2,p38和NF-κB信號傳導,以及通過轉錄因子NF-κB和AP-1的啟動子結合而引起的轉錄激活。IL-10可能通過負反饋迴路自動調節其表達,該迴路涉及IL-10受體的自分泌刺激和p38信號通路的抑制[16]。此外,IL-10的表達在轉錄後水平受到廣泛調控,這可能涉及通過富含AU的元件[17]和諸如let-7[18]或miR-106的microRNA控制mRNA的穩定性[19]

功能

IL-10是一種在免疫調節和炎症中具有多效性的細胞因子。它下調了巨噬細胞上Th1細胞因子、MHC-II類抗原、共刺激分子的表達。它還增強了B細胞的生存、增殖和產生抗體的能力。IL-10可以阻斷NF-kB活動,並參與JAK-STAT信號轉導通路的調節。

IL-10發現與1991年[20],最初報道其抑制細胞分泌、抗原呈遞和CD4+細胞活化。[21][22][23][24]進一步的研究表明,IL-10主要抑制脂多糖(LPS)和細菌產物介導的促炎性細胞因子TNFα[25]、IL-1β[25]、IL-12[26]、IFNγ[27]的分泌,這些細胞因子由Toll樣受體(TLR)觸發的骨髓細胞譜系分泌。

對腫瘤的影響

隨着時間的流逝,IL-10功能的細微差別出現了,因為已證明對荷瘤小鼠的治療可抑制腫瘤轉移[28]。多個實驗室的進一步研究已經產生了進一步支持IL-10在免疫神經學背景下的免疫刺激能力的數據。從IL-10轉基因小鼠[29]中轉染的腫瘤細胞系[30][31]中表達IL-10或用IL-10給藥可控制原發性腫瘤生長並降低轉移負擔。[32][33]最近,聚乙二醇化重組鼠IL-10(PEG-rMuIL-10)已顯示出誘導IFNγ和CD8+T細胞依賴性抗腫瘤免疫力[34][35]。更具體地,已顯示PEG化的重組人IL-10(PEG-rHuIL-10)增強細胞毒性分子粒酶B和穿孔素的CD8+T細胞分泌,並增強T細胞受體依賴性IFNγ的分泌[36]

在疾病中的作用

對小鼠的研究表明,肥大細胞也產生IL-10,抵消了這些細胞在變態反應部位的炎症作用[37]

IL-10能夠抑制由巨噬細胞和Th1T細胞等細胞產生的促炎細胞因子如IFN-γIL-2IL-3TNFαGM-CSF的合成。它也顯示出抑制抗原呈遞細胞的抗原呈遞能力的強大能力。但是,它也對某些T細胞(Th2)和肥大細胞具有刺激性,並刺激B細胞成熟和抗體產生。

IL-10檢查環氧合酶Cyclo-oxygenase-2(COX-2)的可誘導形式。缺乏IL-10已被證明可導致COX激活並導致血栓烷受體激活,從而引起小鼠血管內皮和心臟功能障礙。白介素10基因敲除脆弱的小鼠會隨着年齡的增長而出現心臟和血管功能障礙[38]

IL-10與肌動蛋白有關,因為運動會引起IL-1ra,IL-10和sTNF-R的循環水平增加,這表明體育鍛煉可促進抗炎細胞因子的形成。[39][40]

與健康個體相比,在診斷為多發性硬化症的個體中觀察到較低水平的IL-10[41]。由於IL-10水平的降低,TNFα水平不能得到有效調節,因為IL-10可以調節TNF-α轉化酶[42]。結果,TNFα水平升高並導致炎症。[43]TNFα本身通過TNF受體1誘導少突膠質細胞脫髓鞘,而慢性炎症與神經元脫髓鞘有關。

黑素瘤細胞系中,IL-10調節NKG2D配體的表面表達。[44]

臨床使用或試驗

在小鼠中進行的基因敲除研究表明,這種細胞因子在腸道中是必需的免疫調節劑。[45]的確,克羅恩氏病患者對用重組白介素10產生細菌的治療反應良好,證明了IL-10對抵消人體過度活躍的免疫反應的重要性。[46]

根據數據,在臨床試驗中,數千名患有各種自身免疫性疾病的患者接受了重組人IL-10(rHuIL-10)的治療。與預期相反,rHuIL-10治療並未對克羅恩病患者的疾病產生重大影響。[47][48][49]或類風濕關節炎。[50]rHuIL-10治療最初在牛皮癬中顯示出有希望的臨床數據。[51]但在一項隨機,雙盲,安慰劑對照的II期臨床試驗中未能達到臨床意義。[52]對rHuIL-10在人類中作用的進一步研究表明,rHuIL-10除了抑制炎症外,還能夠發揮促炎作用。[53][54]

聚乙二醇化形式

除這些數據外,目前正在進行一項I期免疫科學臨床試驗,以評估PEG化重組人IL-10(PEG-rHuIL-10,AM0010)的治療能力。[55]與臨床前免疫免疫學數據一致,研究者報告了實質性的抗腫瘤功效。相反於所報告的在體外和體內產生的IL-10的免疫抑制作用,[22][23][24][56][57]治療癌症患者的PEG-重組人白介-10引發的劑量滴定感應的免疫刺激細胞因子IFNγ,IL-18,IL-7,GM-CSF和IL-4的表達。此外,接受治療的患者的外周CD8+T細胞表達活化標記,例如程序性死亡配體1(PD-L1)+,淋巴細胞活化基因3(LAG3)+和Fas配體(FasL)升高,血清TGFβ降低,其摺疊倍數增加。這些發現與使用PEG-rMuIL-10的已發表的臨床前免疫科學報告[34][35]以及以前用rHuIL-10治療人類的發現一致。[53][54]這些數據表明,儘管IL-10可以在細菌產物刺激的髓樣細胞中發揮免疫抑制作用,但對人的rHuIL-10/PEG-rHuIL-10治療主要是免疫刺激。截至2018年 (2018-Missing required parameter 1=month!)AM0010(又名pegilodecakin)正在進行3期臨床試驗。[58]

互動

已經證明IL-10與白介素10受體α亞基相互作用[59][60][61][62][63]

IL-10受體複合物也需要IL10R2鏈來啟動信號傳導。這種配體-受體的組合存在於鳥類和青蛙中,也可能存在於骨魚類中。 

參考資料


  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可免費查閱. 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可免費查閱. 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可免費查閱. 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可免費查閱. 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 (英語). 
  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可免費查閱. 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可免費查閱. 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可免費查閱. 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可免費查閱. 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可免費查閱. 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可免費查閱. 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可免費查閱. 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可免費查閱. 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可免費查閱. 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可免費查閱. 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]. (原始內容 (vanc)存檔於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]. (原始內容存檔於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可免費查閱. 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. 

進一步閱讀

外部連結