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. 1998 Feb 16;17(4):1006–1018. doi: 10.1093/emboj/17.4.1006

IL-10 inhibits macrophage activation and proliferation by distinct signaling mechanisms: evidence for Stat3-dependent and -independent pathways.

A M O'Farrell 1, Y Liu 1, K W Moore 1, A L Mui 1
PMCID: PMC1170450  PMID: 9463379

Abstract

Interleukin-10 (IL-10) limits inflammatory responses by inhibiting macrophage activation. In macrophages, IL-10 activates Stat1 and Stat3. We characterized IL-10 responses of the J774 mouse macrophage cell line, and of J774 cells expressing wild-type hIL-10R, mutant hIL-10R lacking two membrane-distal tyrosines involved in recruitment of Stat3 (hIL-10R-TyrFF), a truncated Stat3 (DeltaStat3) which acts as a dominant negative, or an inducibly active Stat3-gyraseB chimera (Stat3-GyrB). A neutralizing anti-mIL-10R monoclonal antibody was generated to block the function of endogenous mIL-10R. IL-10 inhibited proliferation of J774 cells and of normal bone marrow-derived macrophages, but not J774 cells expressing hIL-10RTyrFF. Dimerization of Stat3-GyrB by coumermycin mimicked the effect of IL-10, and expression of DeltaStat3 blocked the anti-proliferative activity of IL-10. For macrophage de-activation responses, hIL10R-TyrFF could not mediate inhibition of lipopolysaccharide-induced TNFalpha, IL-1beta or CD86 expression, while DeltaStat3 did not interfere detectably with these IL-10 responses. Thus signals mediating both anti-proliferative and macrophage de-activation responses to IL-10 require the two membrane-distal tyrosines of IL-10R, but Stat3 appears to function only in the anti-proliferative response.

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Selected References

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  1. Ali J. A., Orphanides G., Maxwell A. Nucleotide binding to the 43-kilodalton N-terminal fragment of the DNA gyrase B protein. Biochemistry. 1995 Aug 1;34(30):9801–9808. doi: 10.1021/bi00030a018. [DOI] [PubMed] [Google Scholar]
  2. Ascherman D. P., Migone T. S., Friedmann M. C., Leonard W. J. Interleukin-2 (IL-2)-mediated induction of the IL-2 receptor alpha chain gene. Critical role of two functionally redundant tyrosine residues in the IL-2 receptor beta chain cytoplasmic domain and suggestion that these residues mediate more than Stat5 activation. J Biol Chem. 1997 Mar 28;272(13):8704–8709. doi: 10.1074/jbc.272.13.8704. [DOI] [PubMed] [Google Scholar]
  3. Berg D. J., Leach M. W., Kühn R., Rajewsky K., Müller W., Davidson N. J., Rennick D. Interleukin 10 but not interleukin 4 is a natural suppressant of cutaneous inflammatory responses. J Exp Med. 1995 Jul 1;182(1):99–108. doi: 10.1084/jem.182.1.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bhattacharya S., Eckner R., Grossman S., Oldread E., Arany Z., D'Andrea A., Livingston D. M. Cooperation of Stat2 and p300/CBP in signalling induced by interferon-alpha. Nature. 1996 Sep 26;383(6598):344–347. doi: 10.1038/383344a0. [DOI] [PubMed] [Google Scholar]
  5. Briend E., Colle J. H., Fontan E., Saklani-Jusforgues H., Fauve R. M. Human glycoprotein HGP92 induces cytokine synthesis in mouse mononuclear phagocytes. Int Immunol. 1995 Nov;7(11):1753–1761. doi: 10.1093/intimm/7.11.1753. [DOI] [PubMed] [Google Scholar]
  6. Bromberg J. F., Horvath C. M., Wen Z., Schreiber R. D., Darnell J. E., Jr Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon alpha and interferon gamma. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7673–7678. doi: 10.1073/pnas.93.15.7673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bruserud O., Tore Gjertsen B., Brustugun O. T., Bassøe C. F., Nesthus I., Espen Akselsen P., Bühring H. J., Pawelec G. Effects of interleukin 10 on blast cells derived from patients with acute myelogenous leukemia. Leukemia. 1995 Nov;9(11):1910–1920. [PubMed] [Google Scholar]
  8. Chernoff A. E., Granowitz E. V., Shapiro L., Vannier E., Lonnemann G., Angel J. B., Kennedy J. S., Rabson A. R., Wolff S. M., Dinarello C. A. A randomized, controlled trial of IL-10 in humans. Inhibition of inflammatory cytokine production and immune responses. J Immunol. 1995 May 15;154(10):5492–5499. [PubMed] [Google Scholar]
  9. Chin Y. E., Kitagawa M., Su W. C., You Z. H., Iwamoto Y., Fu X. Y. Cell growth arrest and induction of cyclin-dependent kinase inhibitor p21 WAF1/CIP1 mediated by STAT1. Science. 1996 May 3;272(5262):719–722. doi: 10.1126/science.272.5262.719. [DOI] [PubMed] [Google Scholar]
  10. Darnell J. E., Jr, Kerr I. M., Stark G. R. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994 Jun 3;264(5164):1415–1421. doi: 10.1126/science.8197455. [DOI] [PubMed] [Google Scholar]
  11. Ding A. H., Nathan C. F., Stuehr D. J. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol. 1988 Oct 1;141(7):2407–2412. [PubMed] [Google Scholar]
  12. Farrar M. A., Alberol-Ila J., Perlmutter R. M. Activation of the Raf-1 kinase cascade by coumermycin-induced dimerization. Nature. 1996 Sep 12;383(6596):178–181. doi: 10.1038/383178a0. [DOI] [PubMed] [Google Scholar]
  13. Finbloom D. S., Larner A. C., Nakagawa Y., Hoover D. L. Culture of human monocytes with granulocyte-macrophage colony-stimulating factor results in enhancement of IFN-gamma receptors but suppression of IFN-gamma-induced expression of the gene IP-10. J Immunol. 1993 Mar 15;150(6):2383–2390. [PubMed] [Google Scholar]
  14. Finbloom D. S., Winestock K. D. IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes. J Immunol. 1995 Aug 1;155(3):1079–1090. [PubMed] [Google Scholar]
  15. Fluckiger A. C., Durand I., Banchereau J. Interleukin 10 induces apoptotic cell death of B-chronic lymphocytic leukemia cells. J Exp Med. 1994 Jan 1;179(1):91–99. doi: 10.1084/jem.179.1.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fuchs A. C., Granowitz E. V., Shapiro L., Vannier E., Lonnemann G., Angel J. B., Kennedy J. S., Rabson A. R., Radwanski E., Affrime M. B. Clinical, hematologic, and immunologic effects of interleukin-10 in humans. J Clin Immunol. 1996 Sep;16(5):291–303. doi: 10.1007/BF01541395. [DOI] [PubMed] [Google Scholar]
  17. Fujihara M., Ito N., Pace J. L., Watanabe Y., Russell S. W., Suzuki T. Role of endogenous interferon-beta in lipopolysaccharide-triggered activation of the inducible nitric-oxide synthase gene in a mouse macrophage cell line, J774. J Biol Chem. 1994 Apr 29;269(17):12773–12778. [PubMed] [Google Scholar]
  18. Fukada T., Hibi M., Yamanaka Y., Takahashi-Tezuka M., Fujitani Y., Yamaguchi T., Nakajima K., Hirano T. Two signals are necessary for cell proliferation induced by a cytokine receptor gp130: involvement of STAT3 in anti-apoptosis. Immunity. 1996 Nov;5(5):449–460. doi: 10.1016/s1074-7613(00)80501-4. [DOI] [PubMed] [Google Scholar]
  19. Geissler K., Ohler L., Födinger M., Virgolini I., Leimer M., Kabrna E., Kollars M., Skoupy S., Bohle B., Rogy M. Interleukin 10 inhibits growth and granulocyte/macrophage colony-stimulating factor production in chronic myelomonocytic leukemia cells. J Exp Med. 1996 Oct 1;184(4):1377–1384. doi: 10.1084/jem.184.4.1377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Go N. F., Castle B. E., Barrett R., Kastelein R., Dang W., Mosmann T. R., Moore K. W., Howard M. Interleukin 10, a novel B cell stimulatory factor: unresponsiveness of X chromosome-linked immunodeficiency B cells. J Exp Med. 1990 Dec 1;172(6):1625–1631. doi: 10.1084/jem.172.6.1625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gormley N. A., Orphanides G., Meyer A., Cullis P. M., Maxwell A. The interaction of coumarin antibiotics with fragments of DNA gyrase B protein. Biochemistry. 1996 Apr 16;35(15):5083–5092. doi: 10.1021/bi952888n. [DOI] [PubMed] [Google Scholar]
  22. Haspel R. L., Salditt-Georgieff M., Darnell J. E., Jr The rapid inactivation of nuclear tyrosine phosphorylated Stat1 depends upon a protein tyrosine phosphatase. EMBO J. 1996 Nov 15;15(22):6262–6268. [PMC free article] [PubMed] [Google Scholar]
  23. Hattori Y., Akimoto K., Matsumura M., Tseng C. C., Kasai K., Shimoda S. Effect of cycloheximide on the expression of LPS-inducible iNOS, IFN-beta, and IRF-1 genes in J774 macrophages. Biochem Mol Biol Int. 1996 Nov;40(5):889–896. doi: 10.1080/15216549600201503. [DOI] [PubMed] [Google Scholar]
  24. Ho A. S., Liu Y., Khan T. A., Hsu D. H., Bazan J. F., Moore K. W. A receptor for interleukin 10 is related to interferon receptors. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11267–11271. doi: 10.1073/pnas.90.23.11267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ho A. S., Moore K. W. Interleukin-10 and its receptor. Ther Immunol. 1994 Jun;1(3):173–185. [PubMed] [Google Scholar]
  26. Ho A. S., Wei S. H., Mui A. L., Miyajima A., Moore K. W. Functional regions of the mouse interleukin-10 receptor cytoplasmic domain. Mol Cell Biol. 1995 Sep;15(9):5043–5053. doi: 10.1128/mcb.15.9.5043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kim T. K., Maniatis T. Regulation of interferon-gamma-activated STAT1 by the ubiquitin-proteasome pathway. Science. 1996 Sep 20;273(5282):1717–1719. doi: 10.1126/science.273.5282.1717. [DOI] [PubMed] [Google Scholar]
  28. Kitamura T., Onishi M., Kinoshita S., Shibuya A., Miyajima A., Nolan G. P. Efficient screening of retroviral cDNA expression libraries. Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9146–9150. doi: 10.1073/pnas.92.20.9146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kordula T., Travis J. The role of Stat and C/EBP transcription factors in the synergistic activation of rat serine protease inhibitor-3 gene by interleukin-6 and dexamethasone. Biochem J. 1996 Feb 1;313(Pt 3):1019–1027. doi: 10.1042/bj3131019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kühn R., Löhler J., Rennick D., Rajewsky K., Müller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993 Oct 22;75(2):263–274. doi: 10.1016/0092-8674(93)80068-p. [DOI] [PubMed] [Google Scholar]
  31. Lai C. F., Ripperger J., Morella K. K., Jurlander J., Hawley T. S., Carson W. E., Kordula T., Caligiuri M. A., Hawley R. G., Fey G. H. Receptors for interleukin (IL)-10 and IL-6-type cytokines use similar signaling mechanisms for inducing transcription through IL-6 response elements. J Biol Chem. 1996 Jun 14;271(24):13968–13975. doi: 10.1074/jbc.271.24.13968. [DOI] [PubMed] [Google Scholar]
  32. Liu Y., Wei S. H., Ho A. S., de Waal Malefyt R., Moore K. W. Expression cloning and characterization of a human IL-10 receptor. J Immunol. 1994 Feb 15;152(4):1821–1829. [PubMed] [Google Scholar]
  33. Liu Y., de Waal Malefyt R., Briere F., Parham C., Bridon J. M., Banchereau J., Moore K. W., Xu J. The EBV IL-10 homologue is a selective agonist with impaired binding to the IL-10 receptor. J Immunol. 1997 Jan 15;158(2):604–613. [PubMed] [Google Scholar]
  34. Look D. C., Pelletier M. R., Tidwell R. M., Roswit W. T., Holtzman M. J. Stat1 depends on transcriptional synergy with Sp1. J Biol Chem. 1995 Dec 22;270(51):30264–30267. doi: 10.1074/jbc.270.51.30264. [DOI] [PubMed] [Google Scholar]
  35. Ludewig B., Graf D., Gelderblom H. R., Becker Y., Kroczek R. A., Pauli G. Spontaneous apoptosis of dendritic cells is efficiently inhibited by TRAP (CD40-ligand) and TNF-alpha, but strongly enhanced by interleukin-10. Eur J Immunol. 1995 Jul;25(7):1943–1950. doi: 10.1002/eji.1830250722. [DOI] [PubMed] [Google Scholar]
  36. MacNeil I. A., Suda T., Moore K. W., Mosmann T. R., Zlotnik A. IL-10, a novel growth cofactor for mature and immature T cells. J Immunol. 1990 Dec 15;145(12):4167–4173. [PubMed] [Google Scholar]
  37. Meraz M. A., White J. M., Sheehan K. C., Bach E. A., Rodig S. J., Dighe A. S., Kaplan D. H., Riley J. K., Greenlund A. C., Campbell D. Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell. 1996 Feb 9;84(3):431–442. doi: 10.1016/s0092-8674(00)81288-x. [DOI] [PubMed] [Google Scholar]
  38. Minami M., Inoue M., Wei S., Takeda K., Matsumoto M., Kishimoto T., Akira S. STAT3 activation is a critical step in gp130-mediated terminal differentiation and growth arrest of a myeloid cell line. Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):3963–3966. doi: 10.1073/pnas.93.9.3963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Moore K. W., O'Garra A., de Waal Malefyt R., Vieira P., Mosmann T. R. Interleukin-10. Annu Rev Immunol. 1993;11:165–190. doi: 10.1146/annurev.iy.11.040193.001121. [DOI] [PubMed] [Google Scholar]
  40. Mui A. L., Wakao H., Kinoshita T., Kitamura T., Miyajima A. Suppression of interleukin-3-induced gene expression by a C-terminal truncated Stat5: role of Stat5 in proliferation. EMBO J. 1996 May 15;15(10):2425–2433. [PMC free article] [PubMed] [Google Scholar]
  41. Mui A. L., Wakao H., O'Farrell A. M., Harada N., Miyajima A. Interleukin-3, granulocyte-macrophage colony stimulating factor and interleukin-5 transduce signals through two STAT5 homologs. EMBO J. 1995 Mar 15;14(6):1166–1175. doi: 10.1002/j.1460-2075.1995.tb07100.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Nakajima K., Yamanaka Y., Nakae K., Kojima H., Ichiba M., Kiuchi N., Kitaoka T., Fukada T., Hibi M., Hirano T. A central role for Stat3 in IL-6-induced regulation of growth and differentiation in M1 leukemia cells. EMBO J. 1996 Jul 15;15(14):3651–3658. [PMC free article] [PubMed] [Google Scholar]
  43. O'Farrell A. M., Ichihara M., Mui A. L., Miyajima A. Signaling pathways activated in a unique mast cell line where interleukin-3 supports survival and stem cell factor is required for a proliferative response. Blood. 1996 May 1;87(9):3655–3668. [PubMed] [Google Scholar]
  44. Oehler L., Foedinger M., Koeller M., Kollars M., Reiter E., Bohle B., Skoupy S., Fritsch G., Lechner K., Geissler K. Interleukin-10 inhibits spontaneous colony-forming unit-granulocyte-macrophage growth from human peripheral blood mononuclear cells by suppression of endogenous granulocyte-macrophage colony-stimulating factor release. Blood. 1997 Feb 15;89(4):1147–1153. [PubMed] [Google Scholar]
  45. Onishi M., Kinoshita S., Morikawa Y., Shibuya A., Phillips J., Lanier L. L., Gorman D. M., Nolan G. P., Miyajima A., Kitamura T. Applications of retrovirus-mediated expression cloning. Exp Hematol. 1996 Feb;24(2):324–329. [PubMed] [Google Scholar]
  46. Rennick D., Davidson N., Berg D. Interleukin-10 gene knock-out mice: a model of chronic inflammation. Clin Immunol Immunopathol. 1995 Sep;76(3 Pt 2):S174–S178. doi: 10.1016/s0090-1229(95)90144-2. [DOI] [PubMed] [Google Scholar]
  47. Rousset F., Garcia E., Defrance T., Péronne C., Vezzio N., Hsu D. H., Kastelein R., Moore K. W., Banchereau J. Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1890–1893. doi: 10.1073/pnas.89.5.1890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Sadowski H. B., Shuai K., Darnell J. E., Jr, Gilman M. Z. A common nuclear signal transduction pathway activated by growth factor and cytokine receptors. Science. 1993 Sep 24;261(5129):1739–1744. doi: 10.1126/science.8397445. [DOI] [PubMed] [Google Scholar]
  49. Sasse J., Hemmann U., Schwartz C., Schniertshauer U., Heesel B., Landgraf C., Schneider-Mergener J., Heinrich P. C., Horn F. Mutational analysis of acute-phase response factor/Stat3 activation and dimerization. Mol Cell Biol. 1997 Aug;17(8):4677–4686. doi: 10.1128/mcb.17.8.4677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Schaefer T. S., Sanders L. K., Nathans D. Cooperative transcriptional activity of Jun and Stat3 beta, a short form of Stat3. Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9097–9101. doi: 10.1073/pnas.92.20.9097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Schibler K. R., Li Y., Ohls R. K., Nye N. C., Durham M. C., White W., Liechty K. W., Le T., Christensen R. D. Possible mechanisms accounting for the growth factor independence of hematopoietic progenitors from umbilical cord blood. Blood. 1994 Dec 1;84(11):3679–3684. [PubMed] [Google Scholar]
  52. Shuai K., Liao J., Song M. M. Enhancement of antiproliferative activity of gamma interferon by the specific inhibition of tyrosine dephosphorylation of Stat1. Mol Cell Biol. 1996 Sep;16(9):4932–4941. doi: 10.1128/mcb.16.9.4932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Stöcklin E., Wissler M., Gouilleux F., Groner B. Functional interactions between Stat5 and the glucocorticoid receptor. Nature. 1996 Oct 24;383(6602):726–728. doi: 10.1038/383726a0. [DOI] [PubMed] [Google Scholar]
  54. Taga K., Cherney B., Tosato G. IL-10 inhibits apoptotic cell death in human T cells starved of IL-2. Int Immunol. 1993 Dec;5(12):1599–1608. doi: 10.1093/intimm/5.12.1599. [DOI] [PubMed] [Google Scholar]
  55. Taga K., Tosato G. IL-10 inhibits human T cell proliferation and IL-2 production. J Immunol. 1992 Feb 15;148(4):1143–1148. [PubMed] [Google Scholar]
  56. Takeda K., Noguchi K., Shi W., Tanaka T., Matsumoto M., Yoshida N., Kishimoto T., Akira S. Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3801–3804. doi: 10.1073/pnas.94.8.3801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Thompson-Snipes L., Dhar V., Bond M. W., Mosmann T. R., Moore K. W., Rennick D. M. Interleukin 10: a novel stimulatory factor for mast cells and their progenitors. J Exp Med. 1991 Feb 1;173(2):507–510. doi: 10.1084/jem.173.2.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Vieira P., de Waal-Malefyt R., Dang M. N., Johnson K. E., Kastelein R., Fiorentino D. F., deVries J. E., Roncarolo M. G., Mosmann T. R., Moore K. W. Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: homology to Epstein-Barr virus open reading frame BCRFI. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1172–1176. doi: 10.1073/pnas.88.4.1172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Weber-Nordt R. M., Henschler R., Schott E., Wehinger J., Behringer D., Mertelsmann R., Finke J. Interleukin-10 increases Bcl-2 expression and survival in primary human CD34+ hematopoietic progenitor cells. Blood. 1996 Oct 1;88(7):2549–2558. [PubMed] [Google Scholar]
  60. Weber-Nordt R. M., Riley J. K., Greenlund A. C., Moore K. W., Darnell J. E., Schreiber R. D. Stat3 recruitment by two distinct ligand-induced, tyrosine-phosphorylated docking sites in the interleukin-10 receptor intracellular domain. J Biol Chem. 1996 Nov 1;271(44):27954–27961. doi: 10.1074/jbc.271.44.27954. [DOI] [PubMed] [Google Scholar]
  61. Wehinger J., Gouilleux F., Groner B., Finke J., Mertelsmann R., Weber-Nordt R. M. IL-10 induces DNA binding activity of three STAT proteins (Stat1, Stat3, and Stat5) and their distinct combinatorial assembly in the promoters of selected genes. FEBS Lett. 1996 Oct 7;394(3):365–370. doi: 10.1016/0014-5793(96)00990-8. [DOI] [PubMed] [Google Scholar]
  62. Wen Z., Zhong Z., Darnell J. E., Jr Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell. 1995 Jul 28;82(2):241–250. doi: 10.1016/0092-8674(95)90311-9. [DOI] [PubMed] [Google Scholar]
  63. Zhang J. J., Vinkemeier U., Gu W., Chakravarti D., Horvath C. M., Darnell J. E., Jr Two contact regions between Stat1 and CBP/p300 in interferon gamma signaling. Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15092–15096. doi: 10.1073/pnas.93.26.15092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Zhong Z., Wen Z., Darnell J. E., Jr Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science. 1994 Apr 1;264(5155):95–98. doi: 10.1126/science.8140422. [DOI] [PubMed] [Google Scholar]
  65. de Waal Malefyt R., Abrams J., Bennett B., Figdor C. G., de Vries J. E. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991 Nov 1;174(5):1209–1220. doi: 10.1084/jem.174.5.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. de Waal Malefyt R., Yssel H., de Vries J. E. Direct effects of IL-10 on subsets of human CD4+ T cell clones and resting T cells. Specific inhibition of IL-2 production and proliferation. J Immunol. 1993 Jun 1;150(11):4754–4765. [PubMed] [Google Scholar]
  67. te Velde A. A., de Waal Malefijt R., Huijbens R. J., de Vries J. E., Figdor C. G. IL-10 stimulates monocyte Fc gamma R surface expression and cytotoxic activity. Distinct regulation of antibody-dependent cellular cytotoxicity by IFN-gamma, IL-4, and IL-10. J Immunol. 1992 Dec 15;149(12):4048–4052. [PubMed] [Google Scholar]

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