Interferon‐λs: the modulators of antivirus, antitumor, and immune responses

IFN‐λs, including IFN‐λ1, IFN‐λ2, and IFN‐λ3, also known as IL‐29, IL‐28A, or IL‐28B, are a newly described group of cytokines distantly related to the type I IFNs and IL‐10 family members. The IFN‐λR complex consists of a unique ligand‐binding chain, IFN‐λR1 (also designated IL‐28Rα), and an accessory chain, IL‐10R2, which is shared with receptors for IL‐10‐related cytokines. IFN‐λs signal through the IFN‐λR and activate pathways of JAK‐STATs and MAPKs to induce antiviral, antiproliferative, antitumor, and immune responses. In this review, we summarize recent findings about the biology of IFN‐λs and their pathophysiological roles in viral infection, cancer, and immune responses of the innate and adaptive arms.

[1]  J. Melchjorsen,et al.  Human interferon-λ3 is a potent member of the type III interferon family , 2009, Genes and Immunity.

[2]  G. Gallagher,et al.  Interferon‐λ1 (interleukin‐29) preferentially down‐regulates interleukin‐13 over other T helper type 2 cytokine responses in vitro , 2008, Immunology.

[3]  W. Li,et al.  Regulation of apoptosis by type III interferons , 2008, Cell proliferation.

[4]  E. Kroon,et al.  Antiviral activity of type I interferons and interleukins 29 and 28a (type III interferons) against Apeu virus. , 2008, Antiviral research.

[5]  J. Ceuppens,et al.  Type III IFN‐λ mRNA expression in sputum of adult and school‐aged asthmatics , 2008, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[6]  J. Renauld,et al.  Interferon-λ Contributes to Innate Immunity of Mice against Influenza A Virus but Not against Hepatotropic Viruses , 2008, PLoS pathogens.

[7]  M. Fujimoto,et al.  Association of IL-10 receptor 2 (IL10RB) SNP with systemic sclerosis. , 2008, Biochemical and biophysical research communications.

[8]  S. Maher,et al.  IFN-α and IFN-λ differ in their antiproliferative effects and duration of JAK/STAT signaling activity , 2008 .

[9]  J. Lowenthal,et al.  Molecular cloning, expression, and characterization of chicken IFN -lambda. , 2008, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[10]  K. Asadullah,et al.  Maturing dendritic cells are an important source of IL‐29 and IL‐20 that may cooperatively increase the innate immunity of keratinocytes , 2008, Journal of leukocyte biology.

[11]  T. Michiels,et al.  IFN-Lambda (IFN-λ) Is Expressed in a Tissue-Dependent Fashion and Primarily Acts on Epithelial Cells In Vivo , 2008, PLoS pathogens.

[12]  S. Kotenko,et al.  Type III and I interferons increase HIV uptake and replication in human cells that overexpress CD4, CCR5, and CXCR4. , 2008, AIDS research and human retroviruses.

[13]  U. Jensen,et al.  An Important Role for Type III Interferon (IFN-λ/IL-28) in TLR-Induced Antiviral Activity1 , 2008, The Journal of Immunology.

[14]  E. Coccia.  IFN regulation and functions in myeloid dendritic cells. , 2008, Cytokine & growth factor reviews.

[15]  J. Casanova,et al.  Human Toll‐like receptor‐dependent induction of interferons in protective immunity to viruses , 2007, Immunological reviews.

[16]  S. Kotenko,et al.  IFN Regulatory Factor Family Members Differentially Regulate the Expression of Type III IFN (IFN-λ) Genes1 , 2007, The Journal of Immunology.

[17]  S. Johnston.  Innate immunity in the pathogenesis of virus-induced asthma exacerbations. , 2007, Proceedings of the American Thoracic Society.

[18]  S. Smirnov,et al.  Inhibition of type I and type III interferons by a secreted glycoprotein from Yaba-like disease virus , 2007, Proceedings of the National Academy of Sciences.

[19]  S. Kotenko,et al.  Effect of interferon-lambda on replication of hepatitis B virus in human hepatoma cells. , 2007, Virus research.

[20]  T. Michiels,et al.  Type I interferon response in the central nervous system. , 2007, Biochimie.

[21]  G. Uzé,et al.  IL-28 and IL-29: newcomers to the interferon family. , 2007, Biochimie.

[22]  J. Klingström,et al.  Lambda Interferon (IFN-λ) in Serum Is Decreased in Hantavirus-Infected Patients, and In Vitro-Established Infection Is Insensitive to Treatment with All IFNs and Inhibits IFN-γ-Induced Nitric Oxide Production , 2007, Journal of Virology.

[23]  A. Nielsen,et al.  Type III Interferon (IFN) Induces a Type I IFN-Like Response in a Restricted Subset of Cells through Signaling Pathways Involving both the Jak-STAT Pathway and the Mitogen-Activated Protein Kinases , 2007, Journal of Virology.

[24]  J. Casanova,et al.  Induction of MxA Gene Expression by Influenza A Virus Requires Type I or Type III Interferon Signaling , 2007, Journal of Virology.

[25]  Mingcai Li,et al.  On-column refolding purification and characterization of recombinant human interferon-lambda1 produced in Escherichia coli. , 2007, Protein expression and purification.

[26]  Takashi Suzuki,et al.  IL-28 Elicits Antitumor Responses against Murine Fibrosarcoma , 2007, The Journal of Immunology.

[27]  Mingcai Li,et al.  Purification and characterization of prokaryotically expressed human interferon-λ2 , 2007, Biotechnology Letters.

[28]  G. Gallagher,et al.  Human interferon lambda-1 (IFN-λ1/IL-29) modulates the Th1/Th2 response , 2007, Genes and Immunity.

[29]  S. Akira,et al.  Viral Infections Activate Types I and III Interferon Genes through a Common Mechanism* , 2007, Journal of Biological Chemistry.

[30]  G. Gallagher,et al.  Interferon lambda-1 (IFN-λ1/IL-29) induces ELR− CXC chemokine mRNA in human peripheral blood mononuclear cells, in an IFN-γ-independent manner , 2007, Genes and Immunity.

[31]  T. Huang,et al.  Production, characterization, and applications of two novel monoclonal antibodies against human interleukin-28A. , 2006, Tissue antigens.

[32]  Charles M. Rice,et al.  Interferons α and λ Inhibit Hepatitis C Virus Replication With Distinct Signal Transduction and Gene Regulation Kinetics , 2006 .

[33]  A. Billiau.  Interferon: the pathways of discovery I. Molecular and cellular aspects. , 2006, Cytokine & growth factor reviews.

[34]  Pallavur Sivakumar,et al.  Interleukin‐29 uses a type 1 interferon‐like program to promote antiviral responses in human hepatocytes , 2006, Hepatology.

[35]  Stephen T Holgate,et al.  Role of deficient type III interferon-λ production in asthma exacerbations , 2006, Nature Medicine.

[36]  P. Fisher,et al.  The interferon-inducible RNA helicase, mda-5, is involved in measles virus-induced expression of antiviral cytokines. , 2006, Microbes and infection.

[37]  S. Brand,et al.  Novel interferon-λs induce antiproliferative effects in neuroendocrine tumor cells , 2006 .

[38]  M. Ohtsuki,et al.  Antitumor Activity of IFN-λ in Murine Tumor Models1 , 2006, The Journal of Immunology.

[39]  S. Paludan,et al.  IFN-λ: Novel Antiviral Cytokines , 2006 .

[40]  J. Renauld,et al.  Alpha and Lambda Interferon Together Mediate Suppression of CD4 T Cells Induced by Respiratory Syncytial Virus , 2006, Journal of Virology.

[41]  S. Paludan,et al.  Lambda Interferon (IFN-λ), a Type III IFN, Is Induced by Viruses and IFNs and Displays Potent Antiviral Activity against Select Virus Infections In Vivo , 2006, Journal of Virology.

[42]  S. Paludan,et al.  Induction of cytokine expression by herpes simplex virus in human monocyte-derived macrophages and dendritic cells is dependent on virus replication and is counteracted by ICP27 targeting NF-kappaB and IRF-3. , 2006, The Journal of general virology.

[43]  S. Smirnov,et al.  Characterization of the mouse IFN-λ ligand-receptor system: IFN-λs exhibit antitumor activity against B16 melanoma , 2006 .

[44]  Shaoheng He,et al.  Purification and characterization of recombinant human interleukin-29 expressed in Escherichia coli. , 2006, Journal of biotechnology.

[45]  Hai-yan Wang,et al.  Liposome-mediated IL-28 and IL-29 expression in A549 cells and antiviral effect of IL-28 and IL-29 on WISH cells , 2006, Acta Pharmacologica Sinica.

[46]  M. Severa,et al.  Tumor Necrosis Factor Alpha Enhances Influenza A Virus-Induced Expression of Antiviral Cytokines by Activating RIG-I Gene Expression , 2006, Journal of Virology.

[47]  S. Brand,et al.  IL-28A and IL-29 mediate antiproliferative and antiviral signals in intestinal epithelial cells and murine CMV infection increases colonic IL-28A expression. , 2005, American journal of physiology. Gastrointestinal and liver physiology.

[48]  D. Nelson,et al.  Novel type I interferon IL-28A suppresses hepatitis C viral RNA replication , 2005, Virology Journal.

[49]  J. Hiscott,et al.  Gene Expression and Antiviral Activity of Alpha/Beta Interferons and Interleukin-29 in Virus-Infected Human Myeloid Dendritic Cells , 2005, Journal of Virology.

[50]  M. Wadhwa,et al.  Biological activity of interleukins-28 and -29: comparison with type I interferons. , 2005, Cytokine.

[51]  S. Brand,et al.  SOCS-1 inhibits expression of the antiviral proteins 2',5'-OAS and MxA induced by the novel interferon-lambdas IL-28A and IL-29. , 2005, Biochemical and biophysical research communications.

[52]  S. Kotenko,et al.  Murine interferon lambdas (type III interferons) exhibit potent antiviral activity in vivo in a poxvirus infection model. , 2005, The Journal of general virology.

[53]  Y. Kanakura,et al.  IFN‐ζ limitin: a member of type I IFN with mild lympho‐myelosuppression , 2005 .

[54]  S. Meri,et al.  IFN-α Enhances TLR3-Mediated Antiviral Cytokine Expression in Human Endothelial and Epithelial Cells by Up-Regulating TLR3 Expression1 , 2005, The Journal of Immunology.

[55]  F. Chisari,et al.  Lambda Interferon Inhibits Hepatitis B and C Virus Replication , 2005, Journal of Virology.

[56]  I. Julkunen,et al.  IFN-α Regulates TLR-Dependent Gene Expression of IFN-α, IFN-β, IL-28, and IL-291 , 2005, The Journal of Immunology.

[57]  C. D. Krause,et al.  Interferons, interferon‐like cytokines, and their receptors , 2004, Immunological reviews.

[58]  Y. Tomiyama,et al.  Interferon- ζ/Limitin: Novel Type I Interferon That Displays a Narrow Range of Biological Activity , 2004, International journal of hematology.

[59]  L. Adorini.  Immunotherapeutic approaches in multiple sclerosis , 2004, Journal of the Neurological Sciences.

[60]  J. Renauld,et al.  Role of the interleukin (IL)-28 receptor tyrosine residues for antiviral and antiproliferative activity of IL-29/interferon-lambda 1: similarities with type I interferon signaling. , 2004, The Journal of biological chemistry.

[61]  G. Sabatino,et al.  Interleukin-28 and 29 (IL-28 and IL-29): New Cytokines with Anti-Viral Activities , 2004, International journal of immunopathology and pharmacology.

[62]  Peter L. Collins,et al.  Suppression of the Induction of Alpha, Beta, and Gamma Interferons by the NS1 and NS2 Proteins of Human Respiratory Syncytial Virus in Human Epithelial Cells and Macrophages , 2004, Journal of Virology.

[63]  C. D. Krause,et al.  Interleukin-10 and related cytokines and receptors. , 2004, Annual review of immunology.

[64]  E. Coccia,et al.  Viral infection and Toll‐like receptor agonists induce a differential expression of type I and λ interferons in human plasmacytoid and monocyte‐derived dendritic cells , 2004, European journal of immunology.

[65]  S. Kotenko,et al.  The Class II cytokine receptor (CRF2) family: overview and patterns of receptor-ligand interactions. , 2004, Cytokine & growth factor reviews.

[66]  J. Renauld.  Class II cytokine receptors and their ligands: Key antiviral and inflammatory modulators , 2003, Nature Reviews Immunology.

[67]  R. Holmdahl,et al.  IFN-β Gene Deletion Leads to Augmented and Chronic Demyelinating Experimental Autoimmune Encephalomyelitis1 , 2003, The Journal of Immunology.

[68]  H. Hartung,et al.  Immunomodulation in multiple sclerosis: from immunosuppression to neuroprotection. , 2003, Trends in pharmacological sciences.

[69]  D. Lejeune,et al.  Cloning of a new type II cytokine receptor activating signal transducer and activator of transcription (STAT)1, STAT2 and STAT3. , 2003, The Biochemical journal.

[70]  S. Goodbourn,et al.  Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures. , 2000, The Journal of general virology.

[71]  M. Willenbring,et al.  Neuropsychiatric symptoms associated with hepatitis C and interferon alpha: A review. , 2000, The American journal of psychiatry.

[72]  J U Gutterman,et al.  Cytokine therapeutics: lessons from interferon alpha. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[73]  V. Boulay,et al.  A novel and atypical type one interferon gene expressed by trophoblast during early pregnancy. , 1993, The Journal of biological chemistry.

[74]  R. Roberts,et al.  Genes for the trophoblast interferons in sheep, goat, and musk ox and distribution of related genes among mammals. , 1992, Journal of interferon research.

[75]  J. Lindenmann,et al.  Virus interference. I. The interferon , 1957, Proceedings of the Royal Society of London. Series B - Biological Sciences.

[76]  M. Boniotto,et al.  Modulation of the human cytokine response by interferon lambda-1 (IFN-λ1/IL-29) , 2007, Genes and Immunity.

[77]  Christopher B Wilson,et al.  Regulation of interferon-gamma during innate and adaptive immune responses. , 2007, Advances in immunology.

[78]  M. Neurath,et al.  IL-28A is a key regulator of T-cell-mediated liver injury via the T-box transcription factor T-bet. , 2007, Gastroenterology.

[79]  M. Gadina,et al.  The newest interleukins: recent additions to the ever-growing cytokine family. , 2006, Vitamins and hormones.

[80]  Andrew H. Miller,et al.  Neuropsychiatric Adverse Effects of Interferon-α , 2005 .

[81]  A. Lewis-Antes,et al.  IFN-λs mediate antiviral protection through a distinct class II cytokine receptor complex , 2003, Nature Immunology.

[82]  Scott R. Presnell,et al.  IL-28, IL-29 and their class II cytokine receptor IL-28R , 2002, Nature Immunology.