The mechanisms that lead to the psoriatic morphology are not fully elucidated. Several lines of evidence suggest that the positive feedback between keratinocytes and immunocytes plays a key role in the development of the lesions. On the other hand, little information is available on the negative regulatory controls that maintain a new homoeostasis level in psoriatic skin. We suggest here that the interplay of these two contrary feedbacks is likely to entail a hysteresis effect and that psoriasis is likely to be interpreted as a critical phenomenon characterized by a catastrophic shift of the skin from a normal to a hyperplastic state.

Keywords:
Hysteresis, Immunocytes, feedback, Keratinocytes, feedback, Psoriasis, critical phenomenon
1.
Hollox EJ, Huffmeier U, Zeeuwen PL, Palla R, Lascorz J, Rodijk-Olthuis D, van de Kerkhof PC, Traupe H, de Jongh G, den Heijer M, Reis A, Armour JA, Schalkwijk J: Psoriasis is associated with increased beta-defensin genomic copy number. Nat Genet 2008;40:23–25.
2.
Nair RP, Ruether A, Stuart PE, Jenisch S, Tejasvi T, Hiremagalore R, Schreiber S, Kabelitz D, Lim HW, Voorhees JJ, Christophers E, Elder JT, Weichenthal M: Polymorphisms of the IL12B and IL23R genes are associated with psoriasis. J Invest Dermatol 2008;128:1653–1661.
3.
Heenen M, Galand P, de Maertelaer V, Heenen PH: Psoriasis: hyperproliferation cannot induce characteristic epidermal morphology. Cell Tissue Kinet 1987;20:561–570.
4.
Iizuka H, Honda H, Ishida-Yamamoto A: Epidermal remodeling in psoriasis. II. A quantitative analysis of the epidermal architecture. J Invest Dermatol 1997;109:806–810.
5.
Franssen ME, Zeeuwen PL, Vierwinden G, van de Kerkhof PC, Schalkwijk J, van Erp PE: Phenotypical and functional differences in germinative subpopulations derived from normal and psoriatic epidermis. J Invest Dermatol 2005;124:373–383.
6.
Guilhou JJ: Immunopathogenesis of psoriasis: news in an old concept. Dermatology 1998;197:310–312.
7.
Schon MP, Boehncke WH: Psoriasis. N Engl J Med 2005;352:1899–1912.
8.
Krueger G, Ellis CN: Psoriasis – recent advances in understanding its pathogenesis and treatment. J Am Acad Dermatol 2005;53:S94–S100.
9.
Lowes MA, Bowcock AM, Krueger JG: Pathogenesis and therapy of psoriasis. Nature 2007;445:866–873.
10.
Griffiths CE, Barker JN: Pathogenesis and clinical features of psoriasis. Lancet 2007;370:263–271.
11.
Ma HL, Liang S, Li J, Napierata L, Brown T, Benoit S, Senices M, Gill D, Dunussi-Joannopoulos K, Collins M, Nickerson-Nutter C, Fouser LA, Young DA: IL-22 is required for Th17 cell-mediated pathology in a mouse model of psoriasis-like skin inflammation. J Clin Invest 2008;118:597–607.
12.
Hobbs RM, Silva-Vargas V, Groves R, Watt FM: Expression of activated MEK1 in differentiating epidermal cells is sufficient to generate hyperproliferative and inflammatory skin lesions. J Invest Dermatol 2004;123:503–515.
13.
Sano S, Chan KS, Carbajal S, Clifford J, Peavey M, Kiguchi K, Itami S, Nickoloff BJ, Di Giovanni J: Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nat Med 2005;11:43–49.
14.
Voskas D, Jones N, Van Slyke P, Sturk C, Chang W, Haninec A, Babichev YO, Tran J, Master Z, Chen S, Ward N, et al: A cyclosporine-sensitive psoriasis-like disease produced in Tie2 transgenic mice. Am J Pathol 2005;166:843–855.
15.
Heenen M, Simonart T: Biological agents and psoriatic epidermis: what are we ultimately targeting? Dermatology 2006;212:321–323.
16.
Nickoloff BJ: Keratinocytes regain momentum as instigators of cutaneous inflammation. Trends Mol Med 2006;12:102–106.
17.
Simonart T, Heenen M: T cell/keratinocyte interactions in psoriasis: where is the trigger? Br J Dermatol 2007;156:171–172.
18.
van de Kerkhof PC: The evolution of the psoriatic lesion. Br J Dermatol 2007;157:4–15.
19.
Kalayciyan A, Aydemir EH, Kotogyan A: Experimental Koebner phenomenon in patients with psoriasis. Dermatology 2007;215:114–117.
20.
Körver JE, van Duijnhoven MW, Pasch MC, van Erp PE, van de Kerkhof PC: Assessment of epidermal subpopulations and proliferation in healthy skin, symptomless and lesional skin of spreading psoriasis. Br J Dermatol 2006;155:688–694.
21.
Hennings H, Elgjo K: Epidermal regeneration after cellophane tape stripping of hairless mouse skin. Cell Tissue Kinet 1970;3:243–252.
22.
Fisher LB, Maibach HI: Physical occlusion controlling epidermal mitosis. J Invest Dermatol 1972;59:106–108.
23.
Gottlieb AB, Staiano-Coico L, Cohen SR, Varghese M, Carter DM: Occlusive hydrocolloid dressings decrease keratinocyte population growth fraction and clinical scale and skin thickness in active psoriatic plaques. J Dermatol Sci 1990;1:93–96.
24.
Leigh IM, Navsaria H, Purkis PE, McKay IA, Bowden PE, Riddle PN: Keratins (K16 and K17) as markers of keratinocyte hyperproliferation in psoriasis in vivo and in vitro. Br J Dermatol 1995;133:501–511.
25.
Nicolis G, Prigogine I: Self-Organisation in Nonequilibrium Systems. New York, Wiley, 1997.
26.
Keener J, Sneyd J: Mathematical Physiology. New York, Springer, 1998.
27.
Murray JD: Mathematical Biology. I. An Introduction. New York, Springer, 2002.
28.
Lefever R, Lejeune O: Dynamical aspects of immune anti-tumor cytotoxic reactions; in Greppin H, Bronzon M, Degli Agosti R (eds): Some Physicochemical and Mathematical Tools for Understanding of the Living Systems. Geneva, University of Geneva, 1993, pp 169–191.
29.
Lejeune O, Chaplain MAJ, El Akili I: Oscillations and bistability in the dynamics of cytotoxic reactions mediated by the response of immune cells to solid tumours. Math Comput Model 2008;47:649–662.
30.
Goldbeter A: Biochemical Oscillations and Cellular Rhythms. Cambridge, Cambridge University Press, 1996.
31.
Laptev MV, Nikulin NK: Synchronization of oscillations of proliferation of keratinocytes in psoriatic skin by external periodic force: a mathematical model. J Theor Biol 2005;235:485–494.
32.
Takematsu H, Tagami H: Granulocyte-macrophage colony-stimulating factor in psoriasis. Dermatologica 1990;181:16–20.
33.
Tettelbach W, Nanney L, Ellis D, King L, Richmond A: Localization of MGSA/GRO protein in cutaneous lesions. J Cutan Pathol 1993;20:259–266.
34.
Won YH, Sauder DN, McKenzie RC: Cyclosporin A inhibits keratinocyte cytokine gene expression. Br J Dermatol 1994;130:312–319.
35.
Nickoloff BJ: The immunologic and genetic basis of psoriasis. Arch Dermatol 1999;135:1104–1110.
36.
Gillitzer R, Ritter U, Spandau U, Goebeler M, Brocker EB: Differential expression of GRO-alpha and IL-8 mRNA in psoriasis: a model for neutrophil migration and accumulation in vivo. J Invest Dermatol 1996;107:778–782.
37.
Kulke R, Todt-Pingel I, Rademacher D, Rowert J, Schroder JM, Christophers E: Co-localized overexpression of GRO-alpha and IL-8 mRNA is restricted to the suprapapillary layers of psoriatic lesions. J Invest Dermatol 1996;106:526–530.
38.
Steude J, Kulke R, Christophers E: Interleukin-1-stimulated secretion of interleukin-8 and growth-related oncogene-alpha demonstrates greatly enhanced keratinocyte growth in human raft cultured epidermis. J Invest Dermatol 2002;119:1254–1260.
39.
Schmid P, Cox D, McMaster GK, Itin P: In situ hybridization analysis of cytokine, proto-oncogene and tumour suppressor gene expression in psoriasis. Arch Dermatol Res 1993;285:334–340.
40.
Prens EP, Benne K, van Damme J, Bakkus M, Brakel K, Benner R, van Joost T: Interleukin-1 and interleukin-6 in psoriasis. J Invest Dermatol 1990;95:121S–124S.
41.
Castells-Rodellas A, Castell JV, Ramirez-Bosca A, Nicolas JF, Valcuende-Cavero F, Thivolet J: Interleukin-6 in normal skin and psoriasis. Acta Derm Venereol 1992;72:165–168.
42.
Ohta Y, Nishiyama S, Nishioka K: In situ expression of interleukin-6 in psoriatic epidermis during treatment. J Dermatol 1994;21:301–307.
43.
Teunissen MB, Koomen CW, de Waal Malefyt R, Wierenga EA, Bos JD: Interleukin-17 and interferon-gamma synergize in the enhancement of proinflammatory cytokine production by human keratinocytes. J Invest Dermatol 1998;111:645–649.
44.
Funding AT, Johansen C, Kragballe K, Otkjaer K, Jensen UB, Madsen MW, Fjording MS, Finnemann J, Skak-Nielsen T, Paludan SR, Iversen L: Mitogen- and stress-activated protein kinase 1 is activated in lesional psoriatic epidermis and regulates the expression of pro-inflammatory cytokines. J Invest Dermatol 2006;126:1784–1791.
45.
Ozawa M, Terui T, Tagami H: Localization of IL-8 and complement components in lesional skin of psoriasis vulgaris and pustulosis palmaris et plantaris. Dermatology 2005;211:249–255.
46.
Gesser B, Johansen C, Rasmussen MK, Funding AT, Otkjaer K, Kjellerup RB, Kragballe K, Iversen L: Dimethylfumarate specifically inhibits the mitogen and stress-activated kinases 1 and 2 (MSK1/2): possible role for its anti-psoriatic effect. J Invest Dermatol 2007;127:2129–2137.
47.
Dal Pra I, Chiarini A, Pacchiana R, Zumiani G, Zanoni M, Armato U: Comano’s (Trentino) thermal water interferes with tumour necrosis factor-alpha expression and interleukin-8 production and secretion by cultured human psoriatic keratinocytes: yet other mechanisms of its anti-psoriatic action. Int J Mol Med 2007;19:373–379.
48.
Ruckert R, Asadullah K, Seifert M, Budagian VM, Arnold R, Trombotto C, Paus R, Bulfone-Paus S: Inhibition of keratinocyte apoptosis by IL-15: a new parameter in the pathogenesis of psoriasis? J Immunol 2000;165:2240–2250.
49.
Fossiez F, Banchereau J, Murray R, Van Kooten C, Garrone P, Lebecque S: Interleukin-17. Int Rev Immunol 1998;16:541–551.
50.
Li HH, Lin YC, Chen PJ, Hsiao CH, Lee JY, Chen WC, Tzung TY, Wu JC, Chang MS: Interleukin-19 upregulates keratinocyte growth factor and is associated with psoriasis. Br J Dermatol 2005;153:591–595.
51.
Romer J, Hasselager E, Norby PL, Steiniche T, Thorn Clausen J, Kragballe K: Epidermal overexpression of interleukin-19 and -20 mRNA in psoriatic skin disappears after short-term treatment with cyclosporine a or calcipotriol. J Invest Dermatol 2003;121:1306–1311.
52.
Kunz S, Wolk K, Witte E, Witte K, Doecke WD, Volk HD, Sterry W, Asadullah K, Sabat R: Interleukin (IL)-19, IL-20 and IL-24 are produced by and act on keratinocytes and are distinct from classical ILs. Exp Dermatol 2006;15:991–1004.
53.
Sabat R, Wallace E, Endesfelder S, Wolk K: IL-19 and IL-20: two novel cytokines with importance in inflammatory diseases. Expert Opin Ther Targets 2007;11:601–612.
54.
Wei CC, Hsu YH, Li HH, Wang YC, Hsieh MY, Chen WY, Hsing CH, Chang MS: IL-20: biological functions and clinical implications. J Biomed Sci 2006;13:601–612.
55.
Boniface K, Guignouard E, Pedretti N, Garcia M, Delwail A, Bernard FX, Nau F, Guillet G, Dagregorio G, Yssel H, Lecron JC, Morel F: A role for T cell-derived interleukin 22 in psoriatic skin inflammation. Clin Exp Immunol 2007;150:407–415.
56.
Livden JK, Nilsen R, Bjerke JR, Matre R: In situ localization of interferons in psoriatic lesions. Arch Dermatol Res 1989;28:392–397.
57.
McKenzie RC, Sabin E, Szepietowski JC, Gracie JA, Forsey RJ, Howie S: Interferon gamma in keratinocytes in psoriasis. Eur J Dermatol 2003;13:315–316.
58.
Higashiyama M, Hashimoto K, Matsumoto K, Yoshikawa K: Differential expression of transforming growth factor-alpha (TGF-alpha) and EGF receptor in transitional area of psoriatic epidermis. J Dermatol Sci 1994;7:45–53.
59.
Ockenfels HM, Schultewolter T, Ockenfels G, Funk R, Goos M: The antipsoriatic agent dimethylfumarate immunomodulates T-cell cytokine secretion and inhibits cytokines of the psoriatic cytokine network. Br J Dermatol 1998;139:390–395.
60.
Doger FK, Dikicioglu E, Ergin F, Unal E, Sendur N, Uslu M: Nature of cell kinetics in psoriatic epidermis. J Cutan Pathol 2007;34:257–263.
61.
Detmar M, Brown LF, Claffey KP, Yeo KT, Kocher O, Jackman RW, Berse B, Dvorak HF: Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis. J Exp Med 1994;180:1141–1146.
62.
Xia YP, Li B, Hylton D, Detmar M, Yancopoulos GD, Rudge JS: Transgenic delivery of VEGF to mouse skin leads to an inflammatory condition resembling human psoriasis. Blood 2003;102:161–168.
© 2008 S. Karger AG, Basel
2008
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.