Skip to main content

Advertisement

SpringerLink
Log in

Autoimmunity in Psoriasis: Evidence for Specific Autoantigens

  • Psoriasis (J Wu, Section Editor)
  • Published:
Current Dermatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The pathophysiology of psoriasis is highly complex, and the role of autoantigens in psoriasis has been debated for decades. In this article, we examine the evidence in support of psoriasis autoantigens and their contribution to the development of this chronic, inflammatory condition. We also provide an overview of the known biological functions of these psoriasis autoantigens and their potential role in the pathogenesis of psoriatic disease.

Recent Findings

Since 2014, three potential psoriasis autoantigens (LL-37, ADAMTSL5, and PLA2G4D) have been described in the scientific literature.

Summary

Current evidence lends support for the role of autoantigens in psoriasis and offers insights into the underlying mechanisms enabling the breakdown of immune tolerance in the skin. A systematic approach to identify novel psoriasis autoantigens is needed and has the potential to lead to the development of novel interventions and/or treatment strategies, including a possible cure for this condition.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;70(3):512–6. doi:10.1016/j.jaad.2013.11.013.

    Article  PubMed  Google Scholar 

  2. Cohen AD, Dreiher J, Shapiro Y, Vidavsky L, Vardy DA, Davidovici B, et al. Psoriasis and diabetes: a population-based cross-sectional study. J Eur Acad Dermatol Venereol. 2008;22(5):585–9. doi:10.1111/j.1468-3083.2008.02636.x.

    Article  CAS  PubMed  Google Scholar 

  3. Cohen AD, Sherf M, Vidavsky L, Vardy DA, Shapiro J, Meyerovitch J. Association between psoriasis and the metabolic syndrome. A cross-sectional study. Dermatology. 2008;216(2):152–5. doi:10.1159/000111512.

    Article  CAS  PubMed  Google Scholar 

  4. Dreiher J, Weitzman D, Shapiro J, Davidovici B, Cohen AD. Psoriasis and chronic obstructive pulmonary disease: a case-control study. Br J Dermatol. 2008;159(4):956–60. doi:10.1111/j.1365-2133.2008.08749.x.

    Article  CAS  PubMed  Google Scholar 

  5. Gelfand JM, Dommasch ED, Shin DB, Azfar RS, Kurd SK, Wang X, et al. The risk of stroke in patients with psoriasis. J Invest Dermatol. 2009;129(10):2411–8. doi:10.1038/jid.2009.112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296(14):1735–41. doi:10.1001/jama.296.14.1735.

    Article  CAS  PubMed  Google Scholar 

  7. Shalom G, Dreiher J, Cohen A. Psoriasis and obstructive sleep apnea. Int J Dermatol. 2016; doi:10.1111/ijd.13367.

    PubMed  Google Scholar 

  8. Fowler JF, Duh MS, Rovba L, Buteau S, Pinheiro L, Lobo F, et al. The impact of psoriasis on health care costs and patient work loss. J Am Acad Dermatol. 2008;59(5):772–80. doi:10.1016/j.jaad.2008.06.043.

    Article  PubMed  Google Scholar 

  9. Vanderpuye-Orgle J, Zhao Y, Lu J, Shrestha A, Sexton A, Seabury S, et al. Evaluating the economic burden of psoriasis in the United States. J Am Acad Dermatol. 2015;72(6):961–7.e5. doi:10.1016/j.jaad.2015.02.1099.

    Article  PubMed  Google Scholar 

  10. Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med. 2009;361(5):496–509. doi:10.1056/NEJMra0804595.

    Article  CAS  PubMed  Google Scholar 

  11. Ellis CN, Gorsulowsky DC, Hamilton TA, Billings JK, Brown MD, Headington JT, et al. Cyclosporine improves psoriasis in a double-blind study. JAMA. 1986;256(22):3110–6.

    Article  CAS  PubMed  Google Scholar 

  12. Griffiths CE, Powles AV, Leonard JN, Fry L, Baker BS, Valdimarsson H. Clearance of psoriasis with low dose cyclosporin. Br Med J (Clin Res Ed). 1986;293(6549):731–2.

    Article  CAS  Google Scholar 

  13. Ryan TJ, Baker H. Systemic corticosteroids and folic acid antagonists in the treatment of generalized pustular psoriasis. Evaluation and prognosis based on the study of 104 cases. Br J Dermatol. 1969;81(2):134–45.

    Article  CAS  PubMed  Google Scholar 

  14. Bos JD, Hagenaars C, Das PK, Krieg SR, Voorn WJ, Kapsenberg ML. Predominance of “memory” T cells (CD4+, CDw29+) over “naive” T cells (CD4+, CD45R+) in both normal and diseased human skin. Arch Dermatol Res. 1989;281(1):24–30.

    Article  CAS  PubMed  Google Scholar 

  15. Bos JD, Hulsebosch HJ, Krieg SR, Bakker PM, Cormane RH. Immunocompetent cells in psoriasis. In situ immunophenotyping by monoclonal antibodies. Arch Dermatol Res. 1983;275(3):181–9.

    Article  CAS  PubMed  Google Scholar 

  16. Eedy DJ, Burrows D, Bridges JM, Jones FG. Clearance of severe psoriasis after allogenic bone marrow transplantation. BMJ. 1990;300(6729):908.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Krueger GG, Chambers DA, Shelby J. Involved and uninvolved skin from psoriatic subjects: are they equally diseased? Assessment by skin transplanted to congenitally athymic (nude) mice. J Clin Invest. 1981;68(6):1548–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chang JC, Smith LR, Froning KJ, Schwabe BJ, Laxer JA, Caralli LL, et al. CD8+ T cells in psoriatic lesions preferentially use T-cell receptor V beta 3 and/or V beta 13.1 genes. Proc Natl Acad Sci U S A. 1994;91(20):9282–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Baker BS, Griffiths CE, Lambert S, Powles AV, Leonard JN, Valdimarsson H, et al. The effects of cyclosporine A on T lymphocyte and dendritic cell subpopulations in psoriasis. Transplant Proc. 1988;20(3 Suppl 4):72–7.

    CAS  PubMed  Google Scholar 

  20. Mozzanica N, Cattaneo A, Pigatto PD, Finzi AF. Cyclosporine A in psoriasis: an immunohistological study. Transplant Proc. 1988;20(3 Suppl 4):78–84.

    CAS  PubMed  Google Scholar 

  21. Gottlieb AB, Grossman RM, Khandke L, Carter DM, Sehgal PB, Fu SM, et al. Studies of the effect of cyclosporine in psoriasis in vivo: combined effects on activated T lymphocytes and epidermal regenerative maturation. J Invest Dermatol. 1992;98(3):302–9.

    Article  CAS  PubMed  Google Scholar 

  22. • Gottlieb SL, Gilleaudeau P, Johnson R, Estes L, Woodworth TG, Gottlieb AB, et al. Response of psoriasis to a lymphocyte-selective toxin (DAB389IL-2) suggests a primary immune, but not keratinocyte, pathogenic basis. Nat Med. 1995;1(5):442–7. Seminal paper with definitive proof for the role of pathogenic T cells in psoriasis.

    Article  CAS  PubMed  Google Scholar 

  23. Abrams JR, Lebwohl MG, Guzzo CA, Jegasothy BV, Goldfarb MT, Goffe BS, et al. CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris. J Clin Invest. 1999;103(9):1243–52. doi:10.1172/JCI5857.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Krueger GG, Callis KP. Development and use of alefacept to treat psoriasis. J Am Acad Dermatol. 2003;49(2 Suppl):S87–97. doi:10.1016/mjd.2003.552.

    Article  PubMed  Google Scholar 

  25. Lebwohl M, Tyring SK, Hamilton TK, Toth D, Glazer S, Tawfik NH, et al. A novel targeted T-cell modulator, efalizumab, for plaque psoriasis. N Engl J Med. 2003;349(21):2004–13. doi:10.1056/NEJMoa030002.

    Article  CAS  PubMed  Google Scholar 

  26. Menssen A, Trommler P, Vollmer S, Schendel D, Albert E, Gurtler L, et al. Evidence for an antigen-specific cellular immune response in skin lesions of patients with psoriasis vulgaris. J Immunol. 1995;155(8):4078–83.

    CAS  PubMed  Google Scholar 

  27. Harden JL, Hamm D, Gulati N, Lowes MA, Krueger JG. Deep sequencing of the T-cell receptor repertoire demonstrates polyclonal T-cell infiltrates in psoriasis. F1000Res. 2015;4:460. doi:10.12688/f1000research.6756.1.

    PubMed  PubMed Central  Google Scholar 

  28. Kirsch IR, Watanabe R, O’Malley JT, Williamson DW, Scott LL, Elco CP, et al. TCR sequencing facilitates diagnosis and identifies mature T cells as the cell of origin in CTCL. Sci Transl Med. 2015;7(308):308ra158. doi:10.1126/scitranslmed.aaa9122.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Johnston A, Gudjonsson JE, Sigmundsdottir H, Love TJ, Valdimarsson H. Peripheral blood T cell responses to keratin peptides that share sequences with streptococcal M proteins are largely restricted to skin-homing CD8(+) T cells. Clin Exp Immunol. 2004;138(1):83–93. doi:10.1111/j.1365-2249.2004.00600.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Shen Z, Wang G, Fan JY, Li W, Liu YF. HLA DR B1*04, *07-restricted epitopes on keratin 17 for autoreactive T cells in psoriasis. J Dermatol Sci. 2005;38(1):25–39. doi:10.1016/j.jdermsci.2005.01.001.

    Article  CAS  PubMed  Google Scholar 

  31. Jin L, Wang G. Keratin 17: a critical player in the pathogenesis of psoriasis. Med Res Rev. 2014;34(2):438–54. doi:10.1002/med.21291.

    Article  CAS  PubMed  Google Scholar 

  32. Zanetti M. The role of cathelicidins in the innate host defenses of mammals. Curr Issues Mol Biol. 2005;7(2):179–96.

    CAS  PubMed  Google Scholar 

  33. Nagaoka I, Tamura H, Hirata M. An antimicrobial cathelicidin peptide, human CAP18/LL-37, suppresses neutrophil apoptosis via the activation of formyl-peptide receptor-like 1 and P2X7. J Immunol. 2006;176(5):3044–52.

    Article  CAS  PubMed  Google Scholar 

  34. Zasloff M. Antimicrobial peptides of multicellular organisms. Nature. 2002;415(6870):389–95. doi:10.1038/415389a.

    Article  CAS  PubMed  Google Scholar 

  35. • Lande R, Botti E, Jandus C, Dojcinovic D, Fanelli G, Conrad C, et al. The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis. Nat Commun. 2014;5:5621. doi:10.1038/ncomms6621. This study first demonstrated the presence of LL-37 specific T cells, which were found in 46% of patients with psoriasis.

    Article  CAS  PubMed  Google Scholar 

  36. • Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang YH, Homey B, et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature. 2007;449(7162):564–9. doi:10.1038/nature06116. This paper showed that LL-37 complexes with self-DNA leading to TLR activation and subsequent pDC activation.

    Article  CAS  PubMed  Google Scholar 

  37. Zaiou M, Nizet V, Gallo RL. Antimicrobial and protease inhibitory functions of the human cathelicidin (hCAP18/LL-37) prosequence. J Invest Dermatol. 2003;120(5):810–6. doi:10.1046/j.1523-1747.2003.12132.x.

    Article  CAS  PubMed  Google Scholar 

  38. Kreuter A, Jaouhar M, Skrygan M, Tigges C, Stucker M, Altmeyer P, et al. Expression of antimicrobial peptides in different subtypes of cutaneous lupus erythematosus. J Am Acad Dermatol. 2011;65(1):125–33. doi:10.1016/j.jaad.2010.12.012.

    Article  CAS  PubMed  Google Scholar 

  39. Barrat FJ, Meeker T, Gregorio J, Chan JH, Uematsu S, Akira S, et al. Nucleic acids of mammalian origin can act as endogenous ligands for toll-like receptors and may promote systemic lupus erythematosus. J Exp Med. 2005;202(8):1131–9. doi:10.1084/jem.20050914.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Paulsen F, Pufe T, Conradi L, Varoga D, Tsokos M, Papendieck J, et al. Antimicrobial peptides are expressed and produced in healthy and inflamed human synovial membranes. J Pathol. 2002;198(3):369–77. doi:10.1002/path.1224.

    Article  CAS  PubMed  Google Scholar 

  41. Ong PY, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T, et al. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med. 2002;347(15):1151–60. doi:10.1056/NEJMoa021481.

    Article  CAS  PubMed  Google Scholar 

  42. Yamasaki K, Di Nardo A, Bardan A, Murakami M, Ohtake T, Coda A, et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med. 2007;13(8):975–80. doi:10.1038/nm1616.

    Article  CAS  PubMed  Google Scholar 

  43. Kadowaki N, Ho S, Antonenko S, Malefyt RW, Kastelein RA, Bazan F, et al. Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J Exp Med. 2001;194(6):863–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ronnblom L. The importance of the type I interferon system in autoimmunity. Clin Exp Rheumatol. 2016;34(4 Suppl 98):21–4.

    PubMed  Google Scholar 

  45. • Nestle FO, Conrad C, Tun-Kyi A, Homey B, Gombert M, Boyman O, et al. Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production. J Exp Med. 2005;202(1):135–43. doi:10.1084/jem.20050500. This study first demonstrated that pDCs are capable of initiating early psoriasis plaques.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. van der Does AM, Beekhuizen H, Ravensbergen B, Vos T, Ottenhoff TH, van Dissel JT, et al. LL-37 directs macrophage differentiation toward macrophages with a proinflammatory signature. J Immunol. 2010;185(3):1442–9. doi:10.4049/jimmunol.1000376.

    Article  PubMed  Google Scholar 

  47. • Tang X, Basavarajappa D, Haeggstrom JZ, Wan M. P2X7 receptor regulates internalization of antimicrobial peptide LL-37 by human macrophages that promotes intracellular pathogen clearance. J Immunol. 2015;195(3):1191–201. doi:10.4049/jimmunol.1402845. First paper showing the involvement of LL-37 in macrophages.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kawasaki T, Kawai T, Akira S. Recognition of nucleic acids by pattern-recognition receptors and its relevance in autoimmunity. Immunol Rev. 2011;243(1):61–73. doi:10.1111/j.1600-065X.2011.01048.x.

    Article  CAS  PubMed  Google Scholar 

  49. Barton GM, Kagan JC, Medzhitov R. Intracellular localization of toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA. Nat Immunol. 2006;7(1):49–56. doi:10.1038/ni1280.

    Article  CAS  PubMed  Google Scholar 

  50. • Chamilos G, Gregorio J, Meller S, Lande R, Kontoyiannis DP, Modlin RL, et al. Cytosolic sensing of extracellular self-DNA transported into monocytes by the antimicrobial peptide LL37. Blood. 2012;120(18):3699–707. doi:10.1182/blood-2012-01-401364. This study showed that LL-37 could cause an increase in type I IFNs via a TLR-independent manner.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Ganguly D, Chamilos G, Lande R, Gregorio J, Meller S, Facchinetti V, et al. Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J Exp Med. 2009;206(9):1983–94. doi:10.1084/jem.20090480.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Mabuchi T, Hirayama N. Binding affinity and interaction of LL-37 with HLA-C*06:02 in psoriasis. J Invest Dermatol. 2016;136(9):1901–3. doi:10.1016/j.jid.2016.04.033.

    Article  CAS  PubMed  Google Scholar 

  53. Apte SS. A disintegrin-like and metalloprotease (reprolysin-type) with thrombospondin type 1 motif (ADAMTS) superfamily: functions and mechanisms. J Biol Chem. 2009;284(46):31493–7. doi:10.1074/jbc.R109.052340.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Bader HL, Wang LW, Ho JC, Tran T, Holden P, Fitzgerald J, et al. A disintegrin-like and metalloprotease domain containing thrombospondin type 1 motif-like 5 (ADAMTSL5) is a novel fibrillin-1-, fibrillin-2-, and heparin-binding member of the ADAMTS superfamily containing a netrin-like module. Matrix Biol. 2012;31(7–8):398–411. doi:10.1016/j.matbio.2012.09.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. • Arakawa A, Siewert K, Stohr J, Besgen P, Kim SM, Ruhl G, et al. Melanocyte antigen triggers autoimmunity in human psoriasis. J Exp Med. 2015;212(13):2203–12. doi:10.1084/jem.20151093. First paper implicating ADAMTSL5 as a peptide autoantigen in psoriasis.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Conrad C, Boyman O, Tonel G, Tun-Kyi A, Laggner U, de Fougerolles A, et al. Alpha1beta1 integrin is crucial for accumulation of epidermal T cells and the development of psoriasis. Nat Med. 2007;13(7):836–42. doi:10.1038/nm1605.

    Article  CAS  PubMed  Google Scholar 

  57. Abdel-Naser MB, Liakou AI, Elewa R, Hippe S, Knolle J, Zouboulis CC. Increased activity and number of epidermal melanocytes in lesional psoriatic skin. Dermatology. 2016;232(4):425–30. doi:10.1159/000447535.

    Article  CAS  PubMed  Google Scholar 

  58. Bonifacio KM, Kunjravia N, Krueger JG, Fuentes-Duculan J. Cutaneous expression of a disintegrin-like and metalloprotease domain containing thrombospondin type 1 motif-like 5 (ADAMTSL5) in psoriasis goes beyond melanocytes. J Pigment Disord. 2016;3(3). doi:10.4172/2376-0427.1000244.

  59. Chiba H, Michibata H, Wakimoto K, Seishima M, Kawasaki S, Okubo K, et al. Cloning of a gene for a novel epithelium-specific cytosolic phospholipase A2, cPLA2delta, induced in psoriatic skin. J Biol Chem. 2004;279(13):12890–7. doi:10.1074/jbc.M305801200.

    Article  CAS  PubMed  Google Scholar 

  60. Nevalainen TJ. Serum phospholipases A2 in inflammatory diseases. Clin Chem. 1993;39(12):2453–9.

    CAS  PubMed  Google Scholar 

  61. Bourgeois EA, Subramaniam S, Cheng TY, De Jong A, Layre E, Ly D, et al. Bee venom processes human skin lipids for presentation by CD1a. J Exp Med. 2015;212(2):149–63. doi:10.1084/jem.20141505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Subramaniam S, Aslam A, Misbah SA, Salio M, Cerundolo V, Moody DB, et al. Elevated and cross-responsive CD1a-reactive T cells in bee and wasp venom allergic individuals. Eur J Immunol. 2016;46(1):242–52. doi:10.1002/eji.201545869.

    Article  CAS  PubMed  Google Scholar 

  63. Grass DS, Felkner RH, Chiang MY, Wallace RE, Nevalainen TJ, Bennett CF, et al. Expression of human group II PLA2 in transgenic mice results in epidermal hyperplasia in the absence of inflammatory infiltrate. J Clin Invest. 1996;97(10):2233–41. doi:10.1172/JCI118664.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Quaranta M, Knapp B, Garzorz N, Mattii M, Pullabhatla V, Pennino D, et al. Intraindividual genome expression analysis reveals a specific molecular signature of psoriasis and eczema. Sci Transl Med. 2014;6(244):244ra90. doi:10.1126/scitranslmed.3008946.

    Article  PubMed  Google Scholar 

  65. • Cheung KL, Jarrett R, Subramaniam S, Salimi M, Gutowska-Owsiak D, Chen YL, et al. Psoriatic T cells recognize neolipid antigens generated by mast cell phospholipase delivered by exosomes and presented by CD1a. J Exp Med. 2016;213(11):2399–412. doi:10.1084/jem.20160258. This paper was the first to demonstrate that PLA2G4D generates non-peptide neolipid autoantigens in psoriasis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

JEH, JAG, and JGK are supported in part by grant # UL1TR001866 from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program. JEH is also supported in part by grant # KL2TR001865.

Author information

Author notes

  1. Jason E. Hawkes and Jose A. Gonzalez contributed to this work equally and should be considered co-first authors.

Authors and Affiliations

  1. The Laboratory for Investigative Dermatology, The Milstein Research Program, The Rockefeller University, 1230 York Avenue, Box 178, New York, NY, 10065, USA

    Jason E. Hawkes, Jose A. Gonzalez & James G. Krueger

  2. Warren Alpert Medical School, Brown University, Providence, RI, USA

    Jose A. Gonzalez

Authors
  1. Jason E. Hawkes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jose A. Gonzalez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James G. Krueger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James G. Krueger.

Ethics declarations

Conflict of Interest

Jason E. Hawkes and Jose A. Gonzalez declare that they have no conflict of interest.

James G. Krueger has been a consultant to and has received research support from companies that have developed or are developing therapeutics for psoriasis: AbbVie, Amgen, Boehringer, Bristol-Myers Squibb, Celgene, Dermira, Idera, Janssen, Leo, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi, Serono, Sun, Valeant, and Vitae.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Psoriasis

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hawkes, J.E., Gonzalez, J.A. & Krueger, J.G. Autoimmunity in Psoriasis: Evidence for Specific Autoantigens. Curr Derm Rep 6, 104–112 (2017). https://doi.org/10.1007/s13671-017-0177-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13671-017-0177-6

Keywords

Search

Navigation