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PMID: 20392288 Published · ppublish English Introductory Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Overview of the biology of type I interferons.

Arthritis research & therapy ·Vol. 12 Suppl 1 ·2010-00-00 ·Pages S1

Kalliolias GD, Ivashkiv LB

Abstract

Type I interferons are pleiotropic cytokines with antiviral, antitumor and immunoregulatory functions. An aspect of their complex biology is the paradox that, depending on context, type I interferons can be anti-inflammatory and tissue protective or can be proinflammatory and promote autoimmunity. Along these lines, the activation of type I interferon pathways is effective in suppressing disease activity in patients with multiple sclerosis and in animal models of arthritis and colitis, while there is an expectation that blockade of the same pathways will be beneficial in the treatment of patients with systemic lupus erythematosus.

MeSH Terms
Animals Antineoplastic Agents/therapeutic use Antiviral Agents/therapeutic use Autoimmune Diseases/drug therapy,pathology,physiopathology Disease Models, Animal Humans Immunologic Factors/therapeutic use Inflammation/drug therapy,pathology,physiopathology Inflammatory Bowel Diseases/drug therapy Interferon Type I/adverse effects,classification,physiology,therapeutic use Lupus Erythematosus, Systemic/pathology,physiopathology Multiple Sclerosis/drug therapy Neoplasms/drug therapy Receptor, Interferon alpha-beta/physiology STAT Transcription Factors/metabolism Signal Transduction Vertebrates/metabolism Virus Diseases/drug therapy,physiopathology
Chemicals
Antineoplastic Agents Antiviral Agents Immunologic Factors Interferon Type I STAT Transcription Factors Receptor, Interferon alpha-beta
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kalliolias George D
Arthritis and Tissue Degeneration Program and Department of Medicine, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.
Ivashkiv Lionel B
References (79)
79 references, click to expand
  1. The effects of interferon beta treatment on arthritis.
    Rheumatology (Oxford). 1999 Apr;38(4):362-9 PMID: 10378715
  2. Identification of genes selectively regulated by IFNs in endothelial cells.
    J Immunol. 2007 Jan 15;178(2):1122-35 PMID: 17202376
  3. Interferon-beta1b in multiple sclerosis.
    Expert Rev Neurother. 2007 Mar;7(3):227-39 PMID: 17341170
  4. Interferon-alpha as an immunotherapeutic protein.
    J Leukoc Biol. 2002 Apr;71(4):565-81 PMID: 11927642
  5. The production of IL-1 receptor antagonist in IFN-beta-stimulated human monocytes depends on the activation of phosphatidylinositol 3-kinase but not of STAT1.
    J Immunol. 2005 Mar 1;174(5):2974-80 PMID: 15728510
  6. Treatment with recombinant interferon-beta reduces inflammation and slows cartilage destruction in the collagen-induced arthritis model of rheumatoid arthritis.
    Arthritis Res Ther. 2004;6(3):R239-49 PMID: 15142270
  7. Interferon-beta for treatment of rheumatoid arthritis?
    Arthritis Res. 2002;4(6):346-52 PMID: 12453310
  8. IFN-beta in rheumatoid arthritis.
    Front Biosci. 2004 Sep 01;9:3242-7 PMID: 15353352
  9. Type 1 interferons cool the inflamed brain.
    Immunity. 2008 May;28(5):600-2 PMID: 18482563
  10. How cells respond to interferons.
    Annu Rev Biochem. 1998;67:227-64 PMID: 9759489
  11. A type I interferon signature in monocytes is associated with poor response to interferon-beta in multiple sclerosis.
    Brain. 2009 Dec;132(Pt 12):3353-65 PMID: 19741051
  12. Interferons alpha and beta as immune regulators--a new look.
    Immunity. 2001 Jun;14(6):661-4 PMID: 11420036
  13. Regulation of interferon and Toll-like receptor signaling during macrophage activation by opposing feedforward and feedback inhibition mechanisms.
    Immunol Rev. 2008 Dec;226:41-56 PMID: 19161415
  14. Rheumatoid arthritis subtypes identified by genomic profiling of peripheral blood cells: assignment of a type I interferon signature in a subpopulation of patients.
    Ann Rheum Dis. 2007 Aug;66(8):1008-14 PMID: 17223656
  15. Type I interferons as anti-inflammatory mediators.
    Sci STKE. 2007 Dec 11;2007(416):pe70 PMID: 18073382
  16. Expression of interferon beta in synovial tissue from patients with rheumatoid arthritis: comparison with patients with osteoarthritis and reactive arthritis.
    Ann Rheum Dis. 2005 Dec;64(12):1780-2 PMID: 15878901
  17. Critical role for STAT4 activation by type 1 interferons in the interferon-gamma response to viral infection.
    Science. 2002 Sep 20;297(5589):2063-6 PMID: 12242445
  18. Anti-inflammatory properties of Type I interferons.
    Antiviral Res. 2006 Sep;71(2-3):108-16 PMID: 16626815
  19. Induction of clinical autoimmune disease by therapeutic interferon-alpha.
    Autoimmunity. 2003 Dec;36(8):511-8 PMID: 14984028
  20. Type I interferon modulation of cellular responses to cytokines and infectious pathogens: potential role in SLE pathogenesis.
    Autoimmunity. 2003 Dec;36(8):473-9 PMID: 14984024
  21. DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response.
    Nature. 2007 Jul 26;448(7152):501-5 PMID: 17618271
  22. Type I interferons produced by resident renal cells may promote end-organ disease in autoantibody-mediated glomerulonephritis.
    J Immunol. 2009 Nov 15;183(10):6831-8 PMID: 19864599
  23. Type I interferon in systemic lupus erythematosus and other autoimmune diseases.
    Immunity. 2006 Sep;25(3):383-92 PMID: 16979570
  24. Engagement of the type I interferon receptor on dendritic cells inhibits T helper 17 cell development: role of intracellular osteopontin.
    Immunity. 2008 Jul 18;29(1):68-78 PMID: 18619869
  25. The type I IFN induction pathway constrains Th17-mediated autoimmune inflammation in mice.
    J Clin Invest. 2008 May;118(5):1680-90 PMID: 18382764
  26. Complex modulation of cell type-specific signaling in response to type I interferons.
    Immunity. 2006 Sep;25(3):361-72 PMID: 16979568
  27. Interferon-alpha treatment of female (NZW x BXSB)F(1) mice mimics some but not all features associated with the Yaa mutation.
    Arthritis Rheum. 2009 Apr;60(4):1096-101 PMID: 19333924
  28. Toll-like receptor 2 on inflammatory monocytes induces type I interferon in response to viral but not bacterial ligands.
    Nat Immunol. 2009 Nov;10(11):1200-7 PMID: 19801985
  29. A subtype of multiple sclerosis defined by an activated immune defense program.
    Genes Immun. 2006 Sep;7(6):522-31 PMID: 16837931
  30. Synergistic benefit in inflammatory arthritis by targeting I kappaB kinase epsilon and interferon beta.
    Ann Rheum Dis. 2009 Feb;68(2):257-63 PMID: 18653628
  31. RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-beta.
    Nature. 2002 Apr 18;416(6882):744-9 PMID: 11961557
  32. IFN-beta1a inhibits the secretion of Th17-polarizing cytokines in human dendritic cells via TLR7 up-regulation.
    J Immunol. 2009 Mar 15;182(6):3928-36 PMID: 19265172
  33. Type I interferons (alpha/beta) in immunity and autoimmunity.
    Annu Rev Immunol. 2005;23:307-36 PMID: 15771573
  34. Cutting edge: enhancement of antibody responses through direct stimulation of B and T cells by type I IFN.
    J Immunol. 2006 Feb 15;176(4):2074-8 PMID: 16455962
  35. Twist mediates suppression of inflammation by type I IFNs and Axl.
    J Exp Med. 2006 Aug 7;203(8):1891-901 PMID: 16831897
  36. IFN-beta inhibits human Th17 cell differentiation.
    J Immunol. 2009 Oct 15;183(8):5418-27 PMID: 19783688
  37. Stromal cells and osteoclasts are responsible for exacerbated collagen-induced arthritis in interferon-beta-deficient mice.
    Arthritis Rheum. 2005 Dec;52(12):3739-48 PMID: 16320324
  38. TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta.
    Nat Immunol. 2008 Apr;9(4):361-8 PMID: 18297073
  39. Local delivery of beta interferon using an adeno-associated virus type 5 effectively inhibits adjuvant arthritis in rats.
    J Gen Virol. 2007 Jun;88(Pt 6):1717-1721 PMID: 17485531
  40. A weak signal for strong responses: interferon-alpha/beta revisited.
    Nat Rev Mol Cell Biol. 2001 May;2(5):378-86 PMID: 11331912
  41. Proliferative lesions and metalloproteinase activity in murine lupus nephritis mediated by type I interferons and macrophages.
    Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3012-7 PMID: 20133703
  42. TNF activates an IRF1-dependent autocrine loop leading to sustained expression of chemokines and STAT1-dependent type I interferon-response genes.
    Nat Immunol. 2008 Apr;9(4):378-87 PMID: 18345002
  43. TAM receptors are pleiotropic inhibitors of the innate immune response.
    Cell. 2007 Dec 14;131(6):1124-36 PMID: 18083102
  44. Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors.
    Immunity. 2006 Sep;25(3):349-60 PMID: 16979567
  45. Fifty years of interferon research: aiming at a moving target.
    Immunity. 2006 Sep;25(3):343-8 PMID: 16979566
  46. Interferon-alpha promotes abnormal vasculogenesis in lupus: a potential pathway for premature atherosclerosis.
    Blood. 2007 Oct 15;110(8):2907-15 PMID: 17638846
  47. Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6.
    Immunity. 2003 Aug;19(2):225-34 PMID: 12932356
  48. IFN-alpha priming results in a gain of proinflammatory function by IL-10: implications for systemic lupus erythematosus pathogenesis.
    J Immunol. 2004 May 15;172(10):6476-81 PMID: 15128840
  49. HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses.
    Nature. 2009 Nov 5;462(7269):99-103 PMID: 19890330
  50. A multicentre, randomised, double blind, placebo controlled phase II study of subcutaneous interferon beta-1a in the treatment of patients with active rheumatoid arthritis.
    Ann Rheum Dis. 2005 Jan;64(1):64-9 PMID: 15242865
  51. Activation of the interferon-alpha pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease.
    Arthritis Rheum. 2005 May;52(5):1491-503 PMID: 15880830
  52. Alveolar macrophages are the primary interferon-alpha producer in pulmonary infection with RNA viruses.
    Immunity. 2007 Aug;27(2):240-52 PMID: 17723216
  53. Interferon beta for rheumatoid arthritis: new clothes for an old kid on the block.
    Ann Rheum Dis. 2009 Feb;68(2):157-8 PMID: 19139202
  54. Distinct and nonredundant in vivo functions of IFNAR on myeloid cells limit autoimmunity in the central nervous system.
    Immunity. 2008 May;28(5):675-86 PMID: 18424188
  55. Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus.
    Science. 2001 Nov 16;294(5546):1540-3 PMID: 11711679
  56. Mechanisms of type-I- and type-II-interferon-mediated signalling.
    Nat Rev Immunol. 2005 May;5(5):375-86 PMID: 15864272
  57. Association of the IRF5 risk haplotype with high serum interferon-alpha activity in systemic lupus erythematosus patients.
    Arthritis Rheum. 2008 Aug;58(8):2481-7 PMID: 18668568
  58. Type I interferons in host defense.
    Immunity. 2006 Sep;25(3):373-81 PMID: 16979569
  59. Microarray analysis of interferon-regulated genes in SLE.
    Autoimmunity. 2003 Dec;36(8):481-90 PMID: 14984025
  60. Interferons limit inflammatory responses by induction of tristetraprolin.
    Blood. 2006 Jun 15;107(12):4790-7 PMID: 16514065
  61. A novel type I IFN-producing cell subset in murine lupus.
    J Immunol. 2008 Apr 1;180(7):5101-8 PMID: 18354236
  62. RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate.
    Nat Immunol. 2009 Oct;10(10):1065-72 PMID: 19609254
  63. Toll-like receptor 9-induced type I IFN protects mice from experimental colitis.
    J Clin Invest. 2005 Mar;115(3):695-702 PMID: 15765149
  64. Interferon-lambdas: the modulators of antivirus, antitumor, and immune responses.
    J Leukoc Biol. 2009 Jul;86(1):23-32 PMID: 19304895
  65. Interferons at age 50: past, current and future impact on biomedicine.
    Nat Rev Drug Discov. 2007 Dec;6(12):975-90 PMID: 18049472
  66. Sensitization of IFN-gamma Jak-STAT signaling during macrophage activation.
    Nat Immunol. 2002 Sep;3(9):859-66 PMID: 12172544
  67. A randomized, controlled trial of interferon-beta-1a (Avonex(R)) in patients with rheumatoid arthritis: a pilot study [ISRCTN03626626].
    Arthritis Res Ther. 2004;6(1):R73-R77 PMID: 14979940
  68. The genetics and biology of Irf5-mediated signaling in lupus.
    Autoimmunity. 2007 Dec;40(8):591-601 PMID: 18075793
  69. Amelioration of collagen-induced arthritis and suppression of interferon-gamma, interleukin-12, and tumor necrosis factor alpha production by interferon-beta gene therapy.
    Arthritis Rheum. 1999 Jan;42(1):90-9 PMID: 9920019
  70. Type I interferons for induction of remission in ulcerative colitis.
    Cochrane Database Syst Rev. 2008 Jul 16;(3):CD006790 PMID: 18646167
  71. Amplification of IFN-alpha-induced STAT1 activation and inflammatory function by Syk and ITAM-containing adaptors.
    Nat Immunol. 2004 Nov;5(11):1181-9 PMID: 15467722
  72. Type i interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo.
    Immunity. 2001 Apr;14(4):461-70 PMID: 11336691
  73. Homeostatic role of interferons conferred by inhibition of IL-1-mediated inflammation and tissue destruction.
    J Immunol. 2005 Jul 1;175(1):131-8 PMID: 15972639
  74. RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway.
    Cell. 2009 Aug 7;138(3):576-91 PMID: 19631370
  75. Intraarticular interferon-beta gene therapy ameliorates adjuvant arthritis in rats.
    Hum Gene Ther. 2006 Oct;17(10):985-96 PMID: 16984225
  76. Suppression of the effector phase of inflammatory arthritis by double-stranded RNA is mediated by type I IFNs.
    J Immunol. 2007 Feb 15;178(4):2204-11 PMID: 17277125
  77. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood.
    J Exp Med. 2003 Mar 17;197(6):711-23 PMID: 12642603
  78. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages.
    Nat Immunol. 2005 Nov;6(11):1123-32 PMID: 16200070
  79. Type I interferon signaling in dendritic cells stimulates the development of lymph-node-resident T follicular helper cells.
    Immunity. 2009 Sep 18;31(3):491-501 PMID: 19733096
Article Info
Journal
Arthritis research & therapy
Abbr.
Arthritis Res Ther
ISSN
1478-6362
DOI
10.1186/ar2881
Published
2010-00-00
Epub
2010-00-14
Pages
S1
Language
English
Region
England
NLM ID
101154438
PMCID
PMC2991774
Subset
IM
Grants
NIAID NIH HHS · R01 AI046712-11 · United States
NIAID NIH HHS · R01 AI046712 · United States
NIAID NIH HHS · R01 AI059636-04 · United States
NIAMS NIH HHS · R01 AR050401-06A2 · United States
NIAID NIH HHS · R01 AI046712-10 · United States
NIAID NIH HHS · R01 AI059636-03 · United States
NIAID NIH HHS · R01 AI059636 · United States
NIAMS NIH HHS · R01 AR050401 · United States
NIAMS NIH HHS · R01 AR050401-05 · United States
External Links
PubMed source DOI: 10.1186/ar2881 PMC Full Text View journal details
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