Type III interferons (IFNs): Emerging Master Regulators of Immunity

  • Ioanna E. Galani
  • Ourania Koltsida
  • Evangelos AndreakosEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 850)


Lambda interferons (IFN-λs), type III interferons or interleukins 28 and 29 are the latest addition to the class II cytokine family. They share low homology with the interferon (IFN) and IL-10 cytokine families, yet they exhibit common and unique activities, the full spectrum of which still remains incompletely understood. Although initially described for their antiviral functions, it is now appreciated that IFN-λs also mediate diverse antitumor and immune-modulatory effects, and are key determinants of innate immunity at mucosal sites such as the gastrointestinal and respiratory tracks. Here, we are reviewing the biological functions of IFN-λs, the mechanisms controlling their expression, their downstream effects and their role in the maintenance of homeostasis and disease. We are also exploring the potential application of IFN-λs as novel therapeutics.


Lambda interferons (IFN-λs) Type III interferons Interleukin 28 Interleukin 29 Antiviral activity Mucosal immunity 


  1. Abushahba, W., Balan, M., Castaneda, I., Yuan, Y., Reuhl, K., Raveche, E., De La Torre, A., Lasfar, A., & Kotenko, S. V. (2010). Antitumor activity of type I and type III interferons in BNL hepatoma model. Cancer Immunology, Immunotherapy, 59, 1059–1071.CrossRefPubMedGoogle Scholar
  2. Andreakos, E., & Papadopoulos, N. G. (2014). IL-25: The missing link between allergy, viral infection, and asthma? Science Translational Medicine, 6, 256fs38.CrossRefPubMedGoogle Scholar
  3. Ank, N., West, H., Bartholdy, C., Eriksson, K., Thomsen, A. R., & Paludan, S. R. (2006). Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo. Journal of Virology, 80, 4501–4509.PubMedCentralCrossRefPubMedGoogle Scholar
  4. Ank, N., Iversen, M. B., Bartholdy, C., Staeheli, P., Hartmann, R., Jensen, U. B., Dagnaes-Hansen, F., Thomsen, A. R., Chen, Z., Haugen, H., Klucher, K., & Paludan, S. R. (2008). An important role for type III interferon (IFN-lambda/IL-28) in TLR-induced antiviral activity. Journal of Immunology, 180, 2474–2485.CrossRefGoogle Scholar
  5. Aspinall, R. J., & Pockros, P. J. (2004). The management of side-effects during therapy for hepatitis C. Alimentary Pharmacology and Therapeutics, 20, 917–929.CrossRefPubMedGoogle Scholar
  6. Bandi, P., Pagliaccetti, N. E., & Robek, M. D. (2010). Inhibition of type III interferon activity by orthopoxvirus immunomodulatory proteins. Journal of interferon and cytokine research, 30, 123–134.PubMedCentralCrossRefPubMedGoogle Scholar
  7. Bartlett, N. W., Buttigieg, K., Kotenko, S. V., & Smith, G. L. (2005). Murine interferon lambdas (type III interferons) exhibit potent antiviral activity in vivo in a poxvirus infection model. Journal of General Virology, 86, 1589–1596.CrossRefPubMedGoogle Scholar
  8. Bierne, H., Travier, L., Mahlakoiv, T., Tailleux, L., Subtil, A., Lebreton, A., Paliwal, A., Gicquel, B., Staeheli, P., Lecuit, M., & Cossart, P. (2012). Activation of type III interferon genes by pathogenic bacteria in infected epithelial cells and mouse placenta. PLoS ONE, 7, e39080.PubMedCentralCrossRefPubMedGoogle Scholar
  9. Brand, S., Beigel, F., Olszak, T., Zitzmann, K., Eichhorst, S. T., Otte, J. M., Diebold, J., Diepolder, H., Adler, B., Auernhammer, C. J., Goke, B., & Dambacher, J. (2005a). IL-28A and IL-29 mediate antiproliferative and antiviral signals in intestinal epithelial cells and murine CMV infection increases colonic IL-28A expression. American Journal of Physiology-Gastrointestinal and Liver Physiology, 289, G960-8.CrossRefPubMedGoogle Scholar
  10. Brand, S., Zitzmann, K., Dambacher, J., Beigel, F., Olszak, T., Vlotides, G., Eichhorst, S. T., Goke, B., Diepolder, H., & Auernhammer, C. J. (2005b). SOCS-1 inhibits expression of the antiviral proteins 2',5'-OAS and MxA induced by the novel interferon-lambdas IL-28A and IL-29. Biochemical and Biophysical Research Communications, 331, 543–548.CrossRefPubMedGoogle Scholar
  11. Bullens, D. M., Decraene, A., Dilissen, E., Meyts, I., De Boeck, K., Dupont, L. J., & Ceuppens, J. L. (2008). Type III IFN-lambda mRNA expression in sputum of adult and school-aged asthmatics. Clinical and Experimental Allergy, 38, 1459–1467.CrossRefPubMedGoogle Scholar
  12. Coccia, E. M., Severa, M., Giacomini, E., Monneron, D., Remoli, M. E., Julkunen, I., Cella, M., Lande, R., & Uze, G. (2004). Viral infection and Toll-like receptor agonists induce a differential expression of type I and lambda interferons in human plasmacytoid and monocyte-derived dendritic cells. European Journal of Immunology, 34, 796–805.CrossRefPubMedGoogle Scholar
  13. Contoli, M., Message, S. D., Laza-Stanca, V., Edwards, M. R., Wark, P. A., Bartlett, N. W., Kebadze, T., Mallia, P., Stanciu, L. A., Parker, H. L., Slater, L., Lewis-Antes, A., Kon, O. M., Holgate, S. T., Davies, D. E., Kotenko, S. V., Papi, A., & Johnston, S. L. (2006). Role of deficient type III interferon-lambda production in asthma exacerbations. Nature Medicine, 12, 1023–1026.CrossRefPubMedGoogle Scholar
  14. Dai, J., Megjugorac, N. J., Gallagher, G. E., YU, R. Y., & Gallagher, G. (2009). IFN-lambda1 (IL-29) inhibits GATA3 expression and suppresses Th2 responses in human naive and memory T cells. Blood, 113, 5829–5838.CrossRefPubMedGoogle Scholar
  15. Donnelly, R. P., Sheikh, F., Kotenko, S. V., & Dickensheets, H. (2004). The expanded family of class II cytokines that share the IL-10 receptor-2 (IL-10R2) chain. Journal of Leukocyte Biology, 76, 314–321.CrossRefPubMedGoogle Scholar
  16. Fitzgerald-Bocarsly, P. (1993). Human natural interferon-alpha producing cells. Pharmacology and Therapeutics, 60, 39–62.CrossRefPubMedGoogle Scholar
  17. Fox, B. A., Sheppard, P. O., & O’hara, P. J. (2009). The role of genomic data in the discovery, annotation and evolutionary interpretation of the interferon-lambda family. PLoS One, 4, e4933.PubMedCentralCrossRefPubMedGoogle Scholar
  18. Gad, H. H., Dellgren, C., Hamming, O. J., Vends, S., Paludan, S. R., & Hartmann, R. (2009). Interferon-lambda is functionally an interferon but structurally related to the interleukin-10 family. Journal of Biological Chemistry, 284, 20869–20875.PubMedCentralCrossRefPubMedGoogle Scholar
  19. Garcia-Sastre, A., Egorov, A., Matassov, D., Brandt, S., Levy, D. E., Durbin, J. E., Palese, P., & Muster, T. (1998). Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Virology, 252, 324–330.CrossRefPubMedGoogle Scholar
  20. Ge, D., Fellay, J., Thompson, A. J., Simon, J. S., Shianna, K. V., Urban, T. J., Heinzen, E. L., Qiu, P., Bertelsen, A. H., Muir, A. J., Sulkowski, M., Mchutchison, J. G., & Goldstein, D. B. (2009). Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature, 461, 399–401.CrossRefPubMedGoogle Scholar
  21. Hamming, O. J., Terczynska-Dyla, E., Vieyres, G., Dijkman, R., Jorgensen, S. E., Akhtar, H., Siupka, P., Pietschmann, T., Thiel, V., & Hartmann, R. (2013). Interferon lambda 4 signals via the IFNlambda receptor to regulate antiviral activity against HCV and coronaviruses. EMBO Journal, 32, 3055–3065.PubMedCentralCrossRefPubMedGoogle Scholar
  22. Heinze, B., Frey, S., Mordstein, M., Schmitt-Graff, A., Ehl, S., Buchholz, U. J., Collins, P. L., Staeheli, P., & Krempl, C. D. (2011). Both nonstructural proteins NS1 and NS2 of pneumonia virus of mice are inhibitors of the interferon type I and type III responses in vivo. Journal of Virology, 85, 4071–4084.PubMedCentralCrossRefPubMedGoogle Scholar
  23. Huang, J., Smirnov, S. V., Lewis-Antes, A., Balan, M., LI, W., Tang, S., Silke, G. V., Putz, M. M., Smith, G. L., & Kotenko, S. V. (2007). Inhibition of type I and type III interferons by a secreted glycoprotein from Yaba-like disease virus. Proceedings of the National Academy of Sciences of the United States of America, 104, 9822–9827.PubMedCentralCrossRefPubMedGoogle Scholar
  24. Ioannidis, I., YE, F., Mcnally, B., Willette, M., & Flano, E. (2013). Toll-like receptor expression and induction of type I and type III interferons in primary airway epithelial cells. Journal of Virology, 87, 3261–3270.PubMedCentralCrossRefPubMedGoogle Scholar
  25. Iversen, M. B., Ank, N., Melchjorsen, J., & Paludan, S. R. (2010). Expression of type III interferon (IFN) in the vaginal mucosa is mediated primarily by dendritic cells and displays stronger dependence on NF-kappaB than type I IFNs. Journal of Virology, 84, 4579–4586.PubMedCentralCrossRefPubMedGoogle Scholar
  26. Jewell, N. A., Cline, T., Mertz, S. E., Smirnov, S. V., Flano, E., Schindler, C., Grieves, J. L., Durbin, R. K., Kotenko, S. V., & Durbin, J. E. (2010). Lambda interferon is the predominant interferon induced by influenza A virus infection in vivo. Journal of Virology, 84, 11515–11522.PubMedCentralCrossRefPubMedGoogle Scholar
  27. Jordan, W. J., Eskdale, J., Boniotto, M., Rodia, M., Kellner, D., & Gallagher, G. (2007a). Modulation of the human cytokine response by interferon lambda-1 (IFN-lambda1/IL-29). Genes and Immunity, 8, 13–20.CrossRefPubMedGoogle Scholar
  28. Jordan, W. J., Eskdale, J., Srinivas, S., Pekarek, V., Kelner, D., Rodia, M., & Gallagher, G. (2007b). Human interferon lambda-1 (IFN-lambda1/IL-29) modulates the Th1/Th2 response. Genes and Immunity, 8, 254–261.CrossRefPubMedGoogle Scholar
  29. Karpala, A. J., Morris, K. R., Broadway, M. M., Mcwaters, P. G., O’neil, T. E., Goossens, K. E., Lowenthal, J. W., & Bean, A. G. (2008). Molecular cloning, expression, and characterization of chicken IFN -lambda. Journal of Interferon and Cytokine Research, 28, 341–350.CrossRefPubMedGoogle Scholar
  30. Koltsida, O., Hausding, M., Stavropoulos, A., Koch, S., Tzelepis, G., Ubel, C., Kotenko, S. V., Sideras, P., Lehr, H. A., Tepe, M., Klucher, K. M., Doyle, S. E., Neurath, M. F., Finotto, S., & Andreakos, E. (2011). IL-28A (IFN-lambda2) modulates lung DC function to promote Th1 immune skewing and suppress allergic airway disease. EMBO Molecular Medicine, 3, 348–361.PubMedCentralCrossRefPubMedGoogle Scholar
  31. Kotenko, S. V., Gallagher, G., Baurin, V. V., Lewis-Antes, A., Shen, M., Shah, N. K., Langer, J. A., Sheikh, F., Dickensheets, H., & Donnelly, R. P. (2003). IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nature Immunology, 4, 69–77.CrossRefPubMedGoogle Scholar
  32. Lasfar, A., Lewis-Antes, A., Smirnov, S. V., Anantha, S., Abushahba, W., Tian, B., Reuhl, K., Dickensheets, H., Sheikh, F., Donnelly, R. P., Raveche, E., & Kotenko, S. V. (2006). Characterization of the mouse IFN-lambda ligand-receptor system: IFN-lambdas exhibit antitumor activity against B16 melanoma. Cancer Research, 66, 4468–4477.CrossRefPubMedGoogle Scholar
  33. Lauterbach, H., Bathke, B., Gilles, S., Traidl-Hoffmann, C., Luber, C. A., Fejer, G., Freudenberg, M. A., Davey, G. M., Vremec, D., Kallies, A., WU, L., Shortman, K., Chaplin, P., Suter, M., O’keeffe, M., & Hochrein, H. (2010). Mouse CD8alpha+ DCs and human BDCA3+ DCs are major producers of IFN-lambda in response to poly IC. Journal of Experimental Medicine, 207, 2703–2717.PubMedCentralCrossRefPubMedGoogle Scholar
  34. Lebreton, A., Lakisic, G., Job, V., Fritsch, L., Tham, T. N., Camejo, A., Mattei, P. J., Regnault, B., Nahori, M. A., Cabanes, D., Gautreau, A., Ait-Si-Ali, S., Dessen, A., Cossart, P., & Bierne, H. (2011). A bacterial protein targets the BAHD1 chromatin complex to stimulate type III interferon response. Science, 331, 1319–1321.CrossRefPubMedGoogle Scholar
  35. Levraud, J. P., Boudinot, P., Colin, I., Benmansour, A., Peyrieras, N., Herbomel, P., & Lutfalla, G. (2007). Identification of the zebrafish IFN receptor: implications for the origin of the vertebrate IFN system. Journal of Immunology, 178, 4385–4394.CrossRefGoogle Scholar
  36. Li, W., Lewis-Antes, A., Huang, J., Balan, M., & Kotenko, S. V. (2008). Regulation of apoptosis by type III interferons. Cell Proliferation, 41, 960–979.CrossRefPubMedGoogle Scholar
  37. Maher, S. G., Sheikh, F., Scarzello, A. J., Romero-Weaver, A. L., Baker, D. P., Donnelly, R. P., & Gamero, A. M. (2008). IFNalpha and IFNlambda differ in their antiproliferative effects and duration of JAK/STAT signaling activity. Cancer Biology and Therapy, 7, 1109–1115.PubMedCentralCrossRefPubMedGoogle Scholar
  38. Marcello, T., Grakoui, A., Barba-Spaeth, G., Machlin, E. S., Kotenko, S. V., Macdonald, M. R., & Rice, C. M. (2006). Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics. Gastroenterology, 131, 1887–1898.CrossRefPubMedGoogle Scholar
  39. Marie, I., Durbin, J. E., & LEVY, D. E. (1998). Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7. EMBO Journal, 17, 6660–6669.PubMedCentralCrossRefPubMedGoogle Scholar
  40. Megjugorac, N. J., Gallagher, G. E., & Gallagher, G. (2009). Modulation of human plasmacytoid DC function by IFN-lambda1 (IL-29). Journal of Leukocyte Biology, 86, 1359–1363.CrossRefPubMedGoogle Scholar
  41. Mennechet, F. J., & Uze, G. (2006). Interferon-lambda-treated dendritic cells specifically induce proliferation of FOXP3-expressing suppressor T cells. Blood, 107, 4417–4423.CrossRefPubMedGoogle Scholar
  42. Mordstein, M., Kochs, G., Dumoutier, L., Renauld, J. C., Paludan, S. R., Klucher, K., & Staeheli, P. (2008). Interferon-lambda contributes to innate immunity of mice against influenza A virus but not against hepatotropic viruses. PLoS Pathogens, 4, e1000151.PubMedCentralCrossRefPubMedGoogle Scholar
  43. Mordstein, M., Neugebauer, E., Ditt, V., Jessen, B., Rieger, T., Falcone, V., Sorgeloos, F., Ehl, S., Mayer, D., Kochs, G., Schwemmle, M., Gunther, S., Drosten, C., Michiels, T., & Staeheli, P. (2010). Lambda interferon renders epithelial cells of the respiratory and gastrointestinal tracts resistant to viral infections. Journal of Virology, 84, 5670–5677.PubMedCentralCrossRefPubMedGoogle Scholar
  44. Morrow, M. P., Yan, J., Pankhong, P., Shedlock, D. J., Lewis, M. G., Talbott, K., Toporovski, R., Khan, A. S., Sardesai, N. Y., & Weiner, D. B. (2010). IL-28B/IFN-lambda 3 drives granzyme B loading and significantly increases CTL killing activity in macaques. Molecular Therapy, 18, 1714–1723.PubMedCentralCrossRefPubMedGoogle Scholar
  45. Numasaki, M., Tagawa, M., Iwata, F., Suzuki, T., Nakamura, A., Okada, M., Iwakura, Y., Aiba, S., & Yamaya, M. (2007). IL-28 elicits antitumor responses against murine fibrosarcoma. Journal of Immunology, 178, 5086–5098.CrossRefGoogle Scholar
  46. Odendall, C., Dixit, E., Stavru, F., Bierne, H., Franz, K. M., Durbin, A. F., Boulant, S., Gehrke, L., Cossart, P., & Kagan, J. C. (2014). Diverse intracellular pathogens activate type III interferon expression from peroxisomes. Nature Immunology, 15, 717–726.PubMedCentralCrossRefPubMedGoogle Scholar
  47. Onoguchi, K., Yoneyama, M., Takemura, A., Akira, S., Taniguchi, T., Namiki, H., & Fujita, T. (2007). Viral infections activate types I and III interferon genes through a common mechanism. Journal of Biological Chemistry, 282, 7576–7581.CrossRefPubMedGoogle Scholar
  48. Osterlund, P., Veckman, V., Siren, J., Klucher, K. M., Hiscott, J., Matikainen, S., & Julkunen, I. (2005). Gene expression and antiviral activity of alpha/beta interferons and interleukin-29 in virus-infected human myeloid dendritic cells. Journal of Virology, 79, 9608–9617.PubMedCentralCrossRefPubMedGoogle Scholar
  49. Osterlund, P. I., Pietila, T. E., Veckman, V., Kotenko, S. V., & Julkunen, I. (2007). IFN regulatory factor family members differentially regulate the expression of type III IFN (IFN-lambda) genes. Journal of Immunology, 179, 3434–3442.CrossRefGoogle Scholar
  50. Pekarek, V., Srinivas, S., Eskdale, J., & Gallagher, G. (2007). Interferon lambda-1 (IFN-lambda1/IL-29) induces ELR(-) CXC chemokine mRNA in human peripheral blood mononuclear cells, in an IFN-gamma-independent manner. Genes and Immunity, 8, 177–180.CrossRefPubMedGoogle Scholar
  51. Pott, J., Mahlakoiv, T., Mordstein, M., Duerr, C. U., Michiels, T., Stockinger, S., Staeheli, P., & Hornef, M. W. (2011). IFN-lambda determines the intestinal epithelial antiviral host defense. Proceedings of the National Academy of Sciences of the United States of America, 108, 7944–7949.PubMedCentralCrossRefPubMedGoogle Scholar
  52. Prokunina-Olsson, L., Muchmore, B., Tang, W., Pfeiffer, R. M., Park, H., Dickensheets, H., Hergott, D., Porter-Gill, P., Mumy, A., Kohaar, I., Chen, S., Brand, N., Tarway, M., Liu, L., Sheikh, F., Astemborski, J., Bonkovsky, H. L., Edlin, B. R., Howell, C. D., Morgan, T. R., Thomas, D. L., Rehermann, B., Donnelly, R. P., & O’brien, T. R. (2013). A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nature Genetics, 45, 164–171.PubMedCentralCrossRefPubMedGoogle Scholar
  53. Ramos, E. L. (2010). Preclinical and clinical development of pegylated interferon-lambda 1 in chronic hepatitis C. Journal of Interferon and Cytokine Research, 30, 591–595.CrossRefPubMedGoogle Scholar
  54. Robek, M. D., Boyd, B. S., & Chisari, F. V. (2005). Lambda interferon inhibits hepatitis B and C virus replication. Journal of Virology, 79, 3851–3854.PubMedCentralCrossRefPubMedGoogle Scholar
  55. Rusinova, I., Forster, S., YU, S., Kannan, A., Masse, M., Cumming, H., Chapman, R., & Hertzog, P. J. (2013). Interferome v2.0: an updated database of annotated interferon-regulated genes. Nucleic Acids Research, 41, D1040-6.PubMedCentralCrossRefPubMedGoogle Scholar
  56. Sato, M., Hata, N., Asagiri, M., Nakaya, T., Taniguchi, T., & Tanaka, N. (1998). Positive feedback regulation of type I IFN genes by the IFN-inducible transcription factor IRF-7. FEBS Letters, 441, 106–110.CrossRefPubMedGoogle Scholar
  57. Sato, A., Ohtsuki, M., Hata, M., Kobayashi, E., & Murakami, T. (2006). Antitumor activity of IFN-lambda in murine tumor models. Journal of Immunology, 176, 7686–7694.CrossRefGoogle Scholar
  58. Sheppard, P., Kindsvogel, W., Xu, W., Henderson, K., Schlutsmeyer, S., Whitmore, T. E., Kuestner, R., Garrigues, U., Birks, C., Roraback, J., Ostrander, C., Dong, D., Shin, J., Presnell, S., Fox, B., Haldeman, B., Cooper, E., Taft, D., Gilbert, T., Grant, F. J., Tackett, M., Krivan, W., Mcknight, G., Clegg, C., Foster, D., & Klucher, K. M. (2003). IL-28, IL-29 and their class II cytokine receptor IL-28R. Nature Immunology, 4, 63–68.CrossRefPubMedGoogle Scholar
  59. Siegal, F. P., Kadowaki, N., Shodell, M., Fitzgerald-Bocarsly, P. A., Shah, K., Ho, S., Antonenko, S., & Liu, Y. J. (1999). The nature of the principal type 1 interferon-producing cells in human blood. Science, 284, 1835–1837.CrossRefPubMedGoogle Scholar
  60. Sommereyns, C., Paul, S., Staeheli, P., & Michiels, T. (2008). IFN-lambda (IFN-lambda) is expressed in a tissue-dependent fashion and primarily acts on epithelial cells in vivo. PLoS Pathogens, 4, e1000017.PubMedCentralCrossRefPubMedGoogle Scholar
  61. Spann, K. M., Tran, K. C., Chi, B., Rabin, R. L., & Collins, P. L. (2004). Suppression of the induction of alpha, beta, and lambda interferons by the NS1 and NS2 proteins of human respiratory syncytial virus in human epithelial cells and macrophages [corrected]. Journal of Virology, 78, 4363–4369.PubMedCentralCrossRefPubMedGoogle Scholar
  62. Thomas, D. L., Thio, C. L., Martin, M. P., QI, Y., GE, D., O’huigin, C., Kidd, J., Kidd, K., Khakoo, S. I., Alexander, G., Goedert, J. J., Kirk, G. D., Donfield, S. M., Rosen, H. R., Tobler, L. H., Busch, M. P., Mchutchison, J. G., Goldstein, D. B., & Carrington, M. (2009). Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature, 461, 798–801.PubMedCentralCrossRefPubMedGoogle Scholar
  63. Thomson, S. J., Goh, F. G., Banks, H., Krausgruber, T., Kotenko, S. V., Foxwell, B. M., & Udalova, I. A. (2009). The role of transposable elements in the regulation of IFN-lambda1 gene expression. Proceedings of the National Academy of Sciences of the United States of America, 106, 11564–11569.PubMedCentralCrossRefPubMedGoogle Scholar
  64. Wang, J., Oberley-Deegan, R., Wang, S., Nikrad, M., Funk, C. J., Hartshorn, K. L., & Mason, R. J. (2009). Differentiated human alveolar type II cells secrete antiviral IL-29 (IFN-lambda 1) in response to influenza A infection. Journal of Immunology, 182, 1296–1304.CrossRefGoogle Scholar
  65. Wei, H., Wang, S., Chen, Q., Chen, Y., Chi, X., Zhang, L., Huang, S., Gao, G. F., & Chen, J. L. (2014). Suppression of interferon lambda signaling by SOCS-1 results in their excessive production during influenza virus infection. PLoS Pathogens, 10, e1003845.PubMedCentralCrossRefPubMedGoogle Scholar
  66. Witte, K., Gruetz, G., Volk, H. D., Looman, A. C., Asadullah, K., Sterry, W., Sabat, R., & Wolk, K. (2009). Despite IFN-lambda receptor expression, blood immune cells, but not keratinocytes or melanocytes, have an impaired response to type III interferons: implications for therapeutic applications of these cytokines. Genes and Immunity, 10, 702–714.CrossRefPubMedGoogle Scholar
  67. Yin, Z., Dai, J., Deng, J., Sheikh, F., Natalia, M., Shih, T., Lewis-Antes, A., Amrute, S. B., Garrigues, U., Doyle, S., Donnelly, R. P., Kotenko, S. V., & Fitzgerald-Bocarsly, P. (2012). Type III IFNs are produced by and stimulate human plasmacytoid dendritic cells. Journal of Immunology, 189, 2735–2745.CrossRefGoogle Scholar
  68. Young, H. A., & Bream, J. H. (2007). IFN-gamma: recent advances in understanding regulation of expression, biological functions, and clinical applications. Current Topics in Microbiology and Immunology, 316, 97–117.PubMedGoogle Scholar
  69. Zhou, L., Wang, X., Wang, Y. J., Zhou, Y., Hu, S., Ye, L., Hou, W., Li, H., & Ho, W. Z. (2009). Activation of toll-like receptor-3 induces interferon-lambda expression in human neuronal cells. Neuroscience, 159, 629–637.PubMedCentralCrossRefPubMedGoogle Scholar
  70. Zitzmann, K., Brand, S., Baehs, S., Goke, B., Meinecke, J., Spottl, G., Meyer, H., & Auernhammer, C. J. (2006). Novel interferon-lambdas induce antiproliferative effects in neuroendocrine tumor cells. Biochemical and Biophysical Research Communications, 344, 1334–1341.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Ioanna E. Galani
    • 1
  • Ourania Koltsida
    • 1
  • Evangelos Andreakos
    • 1
    Email author
  1. 1.Department of Immunology, Center for Translational and Clinical ResearchBiomedical Research Foundation, Academy of AthensAthensGreece

Personalised recommendations