Rationale and utility of sub-therapeutic/low dose cytokines and growth factors in dermatology: an overview

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Abstract

The review presents data on a new low-dose medicine approach in several dermatoses such as psoriasis, atopic dermatitis and vitiligo based on the signaling molecules, which are responsible for the cross-talk between the psychoneuroendocrine and immune system and regulate the cellular responses to internal and external stimuli. An imbalance of specific signal molecules leads to inflammatory, allergic and autoimmune disorders. The mechanisms of signal molecules’ action and aspects of Psycho-neuro-endocrine-immunology are presented. Recent studies on efficacy of low-dose medicine along with recommended strategies in psoriasis vulgaris (IL-4, IL-10, IL-11), atopic dermatitis (IL-12, IFNγ), and vitiligo (IL-10, IL-4, anti-IL-1, b-FGF) are observed.

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About the authors

I. Podder

Department of Dermatology, CMSDH

Email: Professor@torellolotti.it
India, Kolkata

R. Sadoughifar

University of Rome G. Marconi; Bidarskincenter

Email: Professor@torellolotti.it
Iran, Islamic Republic of, Tehran; Rome, Italy

M. Goldust

University of Rome G. Marconi; Department of Dermatology of University Hospital Basel

Email: Professor@torellolotti.it
Italy, Rome; Basel, Switzerland

Lotti Torello

University of Rome G. Marconi

Author for correspondence.
Email: Professor@torellolotti.it

Professor of Dermatology of University of Studies of Rome Guglielmo Marconi, Rome, Italy

Italy, Rome

References

  1. Ader R, Cohen N, Felten DL. Brain, behavior, and immunity. Brain Behav Immun. 1987;1(1):1-6.
  2. Ader R, Felten D, Cohen N. Interactions between the brain and the immune system. Annu Rev Pharmacol Toxicol. 1990;30:561-602.
  3. Ader R, Cohen N. Psychoneuroimmunology: conditioning and stress. Annu Rev Psychol. 1993;44:53-85.
  4. Ader R, Cohen N, Felten D. Psychoneuroimmunology: interactions between the nervous system and the immune system. Lancet. 1995;345(8942):99-103.
  5. Haroon E, Raison CL, Miller AH. Psychoneuroimmunology meets neuropsychopharmacology: translational implications of the impact of inflammation on behavior. Neuropsychopharmacology. 2012;37(1):137-62.
  6. Ngoc PL, Gold DR, Tzianabos AO, Weiss ST, Celedón JC. Cytokines, allergy, and asthma. Curr Opin Allergy Clin Immunol. 2005;5(2):161-6.
  7. Lourenco EV, La Cava A. Cytokines in systemic lupus erythematosus. Curr Mol Med. 2009;9(3):242-54.
  8. Vandenberg LN, Colborn T, Hayes TB, Heindel JJ, Jacobs DR Jr, Lee DH, et al. Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocr Rev. 2012;33(3):378-455.
  9. Biancotto A, Wank A, Perl S, Cook W, Olnes MJ, Dagur PK, et al. Baseline levels and temporal stability of 27 multiplexed serum cytokine concentrations in healthy subjects. PLoS One. 2013;8(12):e76091.
  10. Olisova OYu, Dodina MI, Kushlinskiy NE. The role of vascular endothelial growth factor in rosacea pathogenesis and it’s medical correction. Russian Journal of Clinical Dermatology and Venereology. 2012;10(1):49-55. (in Russian)
  11. Reeves R, Leonard WJ, Nissen MS. Binding of HMG-I(Y) imparts architectural specificity to a positioned nucleosome on the promoter of the human interleukin-2 receptor alpha gene. Mol Cell Biol. 2000;20(13):4666-79.
  12. Ishihara K, Hirano T. Molecular basis of the cell specificity of cytokine action. Biochim Biophys Acta. 2002;1592(3):281-96.
  13. Commins SP, Borish L, Steinke JW. Immunologic messenger molecules: cytokines, interferons, and chemokines. J Allergy Clin Immunol. 2010;125(2, Suppl 2):S53-72.
  14. Bacchus W, Aubel D, Fussenegger M. Biomedically relevant circuit-design strategies in mammalian synthetic biology. Mol Syst Biol. 2013;9:691.
  15. Weigent DA, Blalock JE. Associations between the neuroendocrine and immune systems. J Leukoc Biol. 1995;58(2):137-50.
  16. Haddad JJ. On the mechanisms and putative pathways involving neuroimmune interactions. Biochem Biophys Res Commun. 2008;370(4):531-5.
  17. De la Fuente M. Editorial: crosstalk between the nervous and the immune systems in health and sickness. Curr Pharm Des. 2014;20(29):4605-7.
  18. Morrell NW, Adnot S, Archer SL, Dupuis J, Jones PL, et al. Cellular and molecular basis of pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54(1 Suppl):S20-31.
  19. Bollyky PL, Bogdani M, Bollyky JB, Hull RL, Wight TN. The role of hyaluronan and the extracellular matrix in islet inflammation and immune regulation. Curr Diab Rep. 2012;12(5):471-80.
  20. Borroni EM, Mantovani A, Locati M, Bonecchi R. Chemokine receptors intracellulartrafficking. Pharmacol Ther. 2010;127(1):1-8.
  21. Farrell MS, Roth BL. Pharmacosynthetics: Reimagining the pharmacogenetic approach. Brain Res. 2013;1511:6-20.
  22. Burnett AF, Biju PG, Lui H, Hauer-Jensen M. Oral interleukin 11 as a countermeasure to lethal total-body irradiation in a murine model. Radiat Res. 2013;180(6):595-602.
  23. Hanson ML, Hixon JA, Li W, Felber BK, Anver MR, Stewart CA, et al. Oral delivery of IL-27 recombinant bacteria attenuates immune colitis in mice. Gastroenterology. 2014;146(1):210-21.e13.
  24. Forster K, Goethel A, Chan CW, Zanello G, Streutker C, Croitoru K. An oral CD3-specific antibody suppresses T-cell-induced colitis and alters cytokine responses to T-cell activation in mice. Gastroenterology. 2012;143(5):1298-307.
  25. Yun Y, Cho YW, Park K. Nanoparticles for oraldelivery: targetednanoparticles with peptidic ligands for oral protein delivery. Adv Drug Deliv Rev. 2013;65(6):822-32.
  26. Epstein OI. Release-activity: a long way from phenomenon to new drugs. Bull Exp Biol Med. 2012;154(1):54-8.
  27. Gariboldi S, Palazzo M, Zanobbio L, Dusio GF, Mauro V, Solimene U, et al. Low dose oraladministration of cytokines for treatment of allergicasthma. Pulm Pharmacol Ther. 2009;22(6):497-510.
  28. D’Amico L, Ruffini E, Ferracini R, Roato I. Low dose of IL-12 stimulates T cell response in cultures of PBMCs derived from non small cell lung cancer patients. J Cancer Ther. 2012;3(4):337-42.
  29. Cardani D, Dusio GF, Luchini P, Sciarabba M, Solimene U, Rumio C. Oral administration of interleukin-10 and anti-IL-1 antibody ameliorates experimental intestinal inflammation. Gastroenterol Res. 2013;6(4):124-33.
  30. Radice E, Miranda V, Bellone G. Low-doses of sequential-kinetic-activated interferon-gamma enhance the ex vivo cytotoxicity of peripheral blood natural killer cells from patients with early-stage colorectal cancer. A preliminary study. Int Immunopharmacol. 2014;19(1):66-73.
  31. Roberti ML, Ricottini L, Capponi A, Sclauzero E, Vicenti P, Fiorentini E, et al. Immunomodulating treatment with low dose Interleukin-4, Interleukin-10 and Interleukin-11 in psoriasisvulgaris. J Biol Regul Homeost Agents. 2014;28(1):133-9.
  32. Luchetti P. Increasing of visual function in patients with retinalatrophytreated with drugs of Low Dose Medicine. Monocentric Retrospective Observational Study. Minerva Oftalmol. 2014;56(3-4):53-61.
  33. Barygina V, Becatti M, Lotti T, Moretti S, Taddei N, Fiorillo C. Treatment with low-dose cytokines reduces oxidative-mediated injury in perilesional keratinocytes from vitiligo skin. J Dermatol Sci. 2015;79(2):163-70.
  34. Lotti T, Hercogova J, Wollina U, Chokoeva AA, Zarrab Z, Gianfaldoni S, et al. Vitiligo: successful combination treatment based on oral low dose cytokines and different topical treatments. J Biol Regul Homeost Agents. 2015;29(1, Suppl):53-8.
  35. Radice E, Bellone G, Miranda V. Enhancement of the Immunostimulatory Functions of ex vivo – Generated Dendritic Cells from Early-Stage Colon Cancer Patients by Consecutive Exposure to Low Doses of Sequential-Kinetic-Activated IL-4 and IL-12. A Preliminary Study. Transl Oncol. 2015;8(4):327-38.
  36. Lotti T. Successful combination treatment for psoriasis with phototherapy and low-dose cytokines: A spontaneous, retrospective observational clinical study. Hautarzt. 2015;66(11):849-54.
  37. Tessaro I, Modina SC, Franciosi F, Sivelli G, Terzaghi L, Lodde V, Luciano AM. Effects of oral administration of low-dose follicle stimulating hormone on hyperandrogenized mice as model of polycystic ovary syndrome. J Ovarian Res. 2015;8:64.
  38. Barygina V, Becatti M, Lotti T, Taddei N, Fiorillo C. Low dose cytokines reduce oxidative stress in primary lesional fibroblasts obtained from psoriatic patients. J Dermatol Sci. 2016;83(3):242-4.
  39. Carello R, Ricottini L, Miranda V, Panei P, Rocchi L. Arcieri R, Galli E. Long term treatment with Low-Dose Medicine in chronicchildhood eczema. A double-blind two-stage randomized control trial. Ital J Pediatr. 2017;43:78.
  40. Genazzani AD, Despini G, Chierchia E, Benedetti C, Prati A. Pharmacological and Integrative Treatment of Stress-Induced Hypothalamic Amenorrhea. In: Genazzani A, Tarlatzis B, eds. Frontiers in Gynecological Endocrinology. ISGE Series. Chapter. Frontiers in Gynecological Endocrinology. ISGE Series. Springer; 2016:69-84. https://doi.org/10.1007/978-3-319-23865-4_9
  41. Castiglioni S, Miranda V, Cazzaniga A, Campanella M, Nichelatti M, Andena M, Maier JAM. Femtograms of interferon γ suffice to modulate the behavior of Jurkat cells: A new light in immunomodulation. Int J Mol Sci. 2017;18(12):2715.
  42. Mancini F, Milardi D, Carfagna P, Grande G, Miranda V, De Cicco Nardone A, et al. Low-dose SKA Progesterone and Interleukin-10 modulate the inflammatory pathway in endometriotic cell lines. Int Immunopharmacol. 2018;55:223-30.
  43. Tagliacarne SC, Valsecchi C, Benazzo M, Nichelatti M, Marseglia A, Ciprandi G, Bernasconi S. Low-dose multicomponent medication modulates humoral and cellular immune response in an ex-vivo study on children subjected to adenoid surgery. Immunol Lett. 2018;203:95-101.
  44. Grandoni M, Perra A, Angileri S, Genitori L. Dolore post-operatorio nella malformazione di Chiari I In eta pediatrica: Arnica compositum versus Levobupivacaine. Anemos Neuroscienze. 2018;29:21-5.
  45. Davies DR, Wlodawer A. Cytokines and their receptor complexes. FASEB J. 1995;9(1):50-6.
  46. Sakamoto S, Caaveiro JM, Sano E, Tanaka Y, Kudou M, Tsumoto K. Contributions of interfacial residues of human Interleukin-15 to the specificity and affinity for its private alpha-receptor. J Mol Biol. 2009;389(5):880-94.
  47. Ezzedine K, Eleftheriadou V, Whitton M, van Geel N. Vitiligo. Lancet. 2015;386(9988):74-84.
  48. Amer AA, Mchepange UO, Gao XH, Hong Y, Qi R, WuY, et al. Hidden victims of childhood vitiligo: impact on parents’ mental health and quality of life. Acta Derm Venereol. 2015;95(3):322-5.
  49. Pahwa P, Mehta M, Khaitan BK, Sharma VK, Ramam M. The psychosocial impact of vitiligo in Indian patients. Indian J Dermatol Venereol Leprol. 2013;79(5):679-85.
  50. Roychoudhuri R, Hirahara K, Mousavi K, Clever D, Klebanoff CA, Bonelli M, et al. BACH2 represses effector programs to stabilize T(reg)-mediated immune homeostasis. Nature. 2013;498(7455):506-10.
  51. Wang CQ, Cruz-Inigo AE, Fuentes-Duculan J, Moussai D, Gulati N, Sullivan-Whalen M, et al. Th17 cells and activated dendritic cells are increased in vitiligo lesions. PLoS One. 2011;6(4):e18907.
  52. Nouri-Koupaee A, Mansouri P, Jahanbini H, Sanati MN, Jadali Z. Differential expression of mRNA for T-bet and GATA-3 transcription factors in peripheral blood mononuclear cells of patients with vitiligo. Clin Exp Dermatol. 2015;40(7):735-40.
  53. Zhou L, Shi YL, Li K, Hamzavi I, Gao TW, Huggins RH, et al. Increased circulating Th17 cells and elevated serum levels of TGF-beta and IL-21 are correlated with human non-segmental vitiligo development. Pigment Cell Melanoma Res. 2015;28(3):324-9.
  54. Laddha NC, Dwivedi M, Begum R. Increased Tumor Necrosis Factor (TNF)-α and its promoter polymorphisms correlate with disease progression and higher susceptibility towards vitiligo. PLoS One. 2012;7(12):e52298.
  55. Zhang Y, Liu L, Jin L, Yi X, Dang E, Yang Y, et al. Oxidative stress-induced calreticulin expression and translocation: new insights into the destruction of melanocytes. J Invest Dermatol. 2014;134(1):183-91.
  56. Lahiri K. Evolution and evaluation of autologous mini punch grafting in vitiligo. Indian J Dermatol. 2009;54(2):159-67.
  57. Marie J, Kovacs D, Pain C, Jouary T, Cota C, Vergier B, et al. Inflammasome activation and vitiligo/nonsegmental vitiligo progression. Br J Dermatol. 2014;170(4):816-23.
  58. Lee AY. Role of keratinocytes in the development of vitiligo. Ann Dermatol. 2012;24(2):115-25.
  59. Lee HS, Goh MJ, Kim J, Choi TJ, Lee HK, Na YJ, Cho KH. A systems-biological study on the identification of safe and effective molecular targets for the reduction of ultraviolet B-induced skin pigmentation. Sci Rep. 2015;5:10305.
  60. Cichorek M, Wachulska M, Stasiewicz A, Tyminska A. Skin melanocytes: biology and development. Postepy Dermatol Alergol. 2013;30(1):30-41.
  61. Ebanks JP, Koshoffer A, Wickett RR, Hakozaki T, Boissy RE. Hydrolytic enzymes of the interfollicular epidermis differ in expression and correlate with the phenotypic difference observed between light and dark skin. J Dermatol. 2013;40(1):27-33.
  62. Van Den Bossche K, Naeyaert JM, Lambert J. The quest for the mechanism of melanin transfer. Traffic. 2006;7(7):769-78.
  63. Scott G, Leopardi S, Parker L, Babiarz L, Seiberg M, Han R. The proteinase-activated receptor-2 mediates phagocytosis in a Rho-dependent manner in human keratinocytes. J Invest Dermatol. 2003;121(3):529-41.
  64. Babiarz-Magee L, Chen N, Seiberg M, Lin CB. The expression and activation of protease-activated receptor-2 correlate with skin color. Pigment Cell Res. 2004;17(3):241-51.
  65. Lotti T, D’Erme AM. Vitiligo as a systemic disease. Clin Dermatol. 2014;32(3):430-4.
  66. Nasti TH, Timares L. Inflammasome activation of IL-1 family mediators in response to cutaneous photodamage. Photochem Photobiol. 2012;88(5):1111-25.
  67. Birol A, Kisa U, Kurtipek GS, Kara F, Kocak M, Erkek E, Caglayan O. Increased tumor necrosis factor alpha (TNF-alpha) and interleukin 1 alpha (IL-1alpha) levels in the lesional skin of patients with nonsegmental vitiligo. Int J Dermatol. 2006;45(8):992-3.
  68. Wang S, Zhou M, Lin F, Liu D Hong W, Lu L, et al. Interferon-γ induces senescence in normal human melanocytes. PLoS One. 2014;9(3):e93232.
  69. Yu HS, Chang KL, Yu CL, Li HF, Wu MT, Wu CS, Wu CS. Alterations in IL-6, IL-8, GM-CSF, TNF-alpha, and IFN-gamma release by peripheral mononuclear cells in patients with active vitiligo. J Invest Dermatol. 1997;108(4):527-9.
  70. Moretti S, Spallanzani A, Amato L, Hautmann G, Gallerani I, Fabiani M, Fabbri P. New insights into the pathogenesis of vitiligo: imbalance of epidermal cytokines at sites of lesions. Pigment Cell Res. 2002;15(2):87-92.
  71. Lee AY, Kim NH, Choi WI, et al. Less keratinocyte-derived factors related to more keratinocyte apoptosis in depigmented than normally pigmented suction-blistered epidermis may cause passive melanocyte death in vitiligo. J Invest Dermatol 2005;124(5):976-83.
  72. Hirobe T, Hasegawa K, Furuya R, Fujiwara R, Sato K. Effects of fibroblast-derived factors on the proliferation and differentiation of human melanocytes in culture. J Dermatol Sci. 2013;71(1):45-57.
  73. Takata T, Tarutani M, Sano S. A failure in endothelin-1 production from vitiligo keratinocytes in response to ultraviolet B irradiation. J Dermatol Sci. 2013;71(3):210-2.
  74. Moretti S, Fabbri P, Baroni G, Berti S, Bani D, Berti E, et al. Keratinocyte dysfunction in vitiligo epidermis: cytokine microenvironment and correlation to keratinocyte apoptosis. Histol Histopathol. 2009;24(7):849-57.
  75. Olisova OYu, Andreeva EV. Once more about hyperpigmentation. Russian Journal of Skin and Venereal Diseases. 2014;17(2):20-4. (in Russian)
  76. Boissy RE, Nordlund JJ. Molecular basis of congenital hypopigmentary disorders in humans: a review. Pigment Cell Res. 1997;10(1-2):12-24.
  77. Hyter S, Coleman DJ, Ganguli-Indra G, Merrill G, Ma S, Yanagisawa M, Indra AK. Endothelin-1 is a transcriptional target of p53 in epidermal keratinocytes and regulates ultraviolet-induced melanocyte homeostasis. Pigment Cell Melanoma Res. 2013;26(2):247-58.
  78. Kitamura R, Tsukamoto K, Harada K, Shimizu A, Shimada S, Kobayashi T, Imokawa G. Mechanisms underlying the dysfunction of melanocytes in vitiligo epidermis: role of SCF/KIT protein interactions and the downstream effector, MITF-M. J Pathol. 2004;202(4):463-75.
  79. Imokawa G. Autocrine and paracrine regulation of melanocytes in human skin and in pigmentary disorders. Pigment Cell Res. 2004;17(2):96-110.
  80. Cheong KA, Noh M, Kim CH, Lee AY. S100B as a potential biomarker for the detection of cytotoxicity of melanocytes. Exp Dermatol. 2014;23(3):165-71.
  81. Terazawa S, Nakajima H, Fukasawa K, Imokawa G. Withaferin A abolishes the stem cell factor-stimulated pigmentation of human epidermal equivalents by interrupting the auto-phosphorylation of c-KIT in human melanocytes. Arch Dermatol Res. 2015;307(1):73-88.
  82. Yamaguchi Y, Hearing VJ. Physiological factors that regulate skin pigmentation. Biofactors. 2009;35(2):193-9.
  83. Wan P, Hu Y, He L. Regulation of melanocyte pivotal transcription factor MITF by some other transcription factors. Mol Cell Biochem. 2011;354(1-2):241-6.
  84. Dong L, Li Y, Cao J, Liu F, Pier E, Chen J, et al. FGF2 regulates melanocytes viability through the STAT3-transactivated PAX3 transcription. Cell Death Differ. 2012;19(4):616-22.
  85. Weiner L, Han R, Scicchitano BM, Li J, Hasegawa K, Grossi M, et al. Dedicated epithelial recipient cells determine pigmentation patterns. Cell. 2007;130(5):932-42.
  86. Elias PM, Menon G, Wetzel BK, Williams JJ. Barrier requirements as the evolutionary “driver” of epidermal pigmentation in humans. Am J Hum Biol. 2010;22(4):526-37.
  87. Hirobe T. Role of keratinocyte-derived factors involved in regulating the proliferation and differentiation of mammalian epidermal melanocytes. Pigment Cell Res. 2005;18(1):2-12.
  88. Wang Z, Zhang H, Xu X, Shi H, Yu X, Wang X, et al. bFGF inhibits ER stress induced by ischemic oxidative injury via activation of the PI3K/Akt and ERK1/2 pathways. Toxicol Lett. 2012;212(2):137-46.
  89. Glassman SJ. Vitiligo, reactive oxygen species and T-cells. Clin Sci (Lond). 2011;120(3):99-120.
  90. Karsli N, Akcali C, Ozgoztasi O, Kirtak N, Inaloz S. Role of oxidative stress in the pathogenesis of vitiligo with special emphasis on the antioxidant action of narrowband ultraviolet B phototherapy. J Int Med Res. 2014;42(3):799-805.
  91. Westerhof W, d’Ischia M. Vitiligo puzzle: the pieces fall in place. Pigment Cell Res. 2007;20(5):345-59.
  92. Thannickal VJ, Day RM, Klinz SG, Bastien MC, Larios JM, Fanburg BL. Ras-dependent and -independent regulation of reactive oxygen species by mitogenic growth factors and TGF-beta1. FASEB J. 2000;14(12):1741-8.
  93. Zhou Z, Li CY, Li K, Wang T, Zhang B, Gao TW. Decreased methionine sulphoxide reductase A expression renders melanocytes more sensitive to oxidative stress: a possible cause for melanocyte loss in vitiligo. Br J Dermatol. 2009;161(3):504-9.
  94. Jain D, Misra R, Kumar A, Jaiswal G. Levels of malondialdehyde and antioxidants in the blood of patients with vitiligo of age group 11-20 years. Indian J Physiol Pharmacol. 2008;52(3):297-301.
  95. Khan R, Satyam A, Gupta S, Sharma VK, Sharma A. Circulatory levels of antioxidants and lipid peroxidation in Indian patients with generalized and localized vitiligo. Arch Dermatol Res. 2009;301(10):731-7.
  96. Kim JY, Kim Do Y, Son H, Kim YJ, Oh SH. Protease-activated receptor-2 activates NQO-1 via Nrf2 stabilization in keratinocytes. J Dermatol Sci. 2014;74(1):48-55.
  97. Kostyuk VA, Potapovich AI, Cesareo E, Brescia S, Guerra L, Valacchi G, et al. Dysfunction of glutathione S-transferase leads to excess 4-hydroxy-2-nonenal and H(2)O(2) and impaired cytokine pattern in cultured keratinocytes and blood of vitiligo patients. Antioxid Redox Signal. 2010;13(5):607-20.
  98. Qiu L, Song Z, Setaluri V. Oxidative stress and vitiligo: the Nrf2-ARE signaling connection. J Invest Dermatol. 2014; 134(8):2074-6.
  99. Marrot L, Jones C, Perez P, Meunier JR. The significance of Nrf2 pathway in (photo)-oxidative stress response in melanocytes and keratinocytes of the human epidermis. Pigment Cell Melanoma Res. 2008;21(1):79-88.
  100. Jian Z, Li K, Liu L, Zhang Y, Zhou Z, Li C, Gao T. Heme oxygenase-1 protects human melanocytes from H2O2-induced oxidative stress via the Nrf2-ARE pathway. J Invest Dermatol. 2011;131(7):1420-7.
  101. Jian Z, Li K, Song P, Zhu G, Zhu L, Cui T, et al. Impaired activation of the Nrf2-ARE signaling pathway undermines H2O2-induced oxidative stress response: a possible mechanism for melanocyte degeneration in vitiligo. J Invest Dermatol. 2014;134(8):2221-30.
  102. Li P, Ma H, Han D, Mou K. Interleukin-33 affects cytokine production by keratinocytes in vitiligo. Clin Exp Dermatol. 2015;40(2):163-70.
  103. Nguyen TV, Cowen EW, Leslie KS. Autoinflammation: From monogenic syndromes to common skin diseases. J Am Acad Dermatol. 2013;68(5):834-53.
  104. Nouri-Koupaee A, Mansouri P, Jahanbini H, Sanati MN, Jadali Z. Differential expression of mRNA for T-bet and GATA-3 transcription factors in peripheral blood mononuclear cells of patients with vitiligo. Clin Exp Dermatol. 2015;40(7):735-40.
  105. Cooke A. Th17 cells in inflammatory conditions. Rev Diabet Stud. 2006;3(2):72-5.
  106. Paul WE, Zhu J. How are T(H)2-type immune responses initiated and amplified? Nat Rev Immunol. 2010;10(4):225-35.
  107. Beebe AM, Cua DJ, de Waal Malefyt R. The role of interleukin-10 in autoimmune disease: systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Cytokine Growth Factor Rev. 2002;13:403-12.
  108. Dinarello CA, van derMeer JW. Treating inflammation by blocking interleukin-1 in humans. Semin Immunol. 2013;25(6):469-84.
  109. Suskova VS, Pinson IYa, Olisova OYu. Immunopathological mechanisms of psoriasis. Russian Journal of Clinical Dermatology and Venereology. 2006;4(1):68-70. (in Russian)
  110. Lotti T, Hercogova J, Fabrizi G. Advances in the treatment options for vitiligo: activated low-dose cytokines-based therapy. Expert Opin Pharmacother. 2015;16(16):2485-96.

Supplementary files

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2. Figure 1. Range of physiological concentration of signaling molecules at the level of the extracellular matrix.

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3. Figure 2. The role of M cells in the processes of absorption of signaling molecules at the level of the intestinal lumen.

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4. Figure 3. Relationship between signaling molecules concentrations and their effects.

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5. Figure 4. Schematic representation of the main intercellular pathways involved in melanocytes growth and differentiation and melanin synthesis under stimulation of keratinocytes-derived signaling molecules (ET, SCF, b-FGF).

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6. Figure 5. Keratinocytes-melanocytes cross-talk. Melanocytes growth and melanin production are impaired in presence of a ROS-mediated inflammatory response mainly driven by the proinflammatory cytokines TNFα, IL-6 and IL-33 (IL-1).

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