Keratinocytes under Fire of Proinflammatory Cytokines: Bona Fide Innate Immune Cells Involved in the Physiopathology of Chronic Atopic Dermatitis and Psoriasis
This article is part of Special Issue:
François-Xavier Bernard,
Franck Morel,
Magalie Camus,
Nathalie Pedretti,
Christine Barrault,
Julien Garnier,
Jean-Claude Lecron,
François-Xavier Bernard
Laboratoire Inflammation, Tissus Épithéliaux et Cytokines, UPRES-EA 4331, CHU de Poitiers, Pole Biologie Santé, Université de Poitiers, Bâtiment B36, 1 rue G Bonnet, 86022 Poitiers, France univ-poitiers.fr
BIOalternatives, 1 bis rue des Plantes, 86160 Gençay, France bioalternatives.com
Search for more papers by this authorFranck Morel
Laboratoire Inflammation, Tissus Épithéliaux et Cytokines, UPRES-EA 4331, CHU de Poitiers, Pole Biologie Santé, Université de Poitiers, Bâtiment B36, 1 rue G Bonnet, 86022 Poitiers, France univ-poitiers.fr
Search for more papers by this authorMagalie Camus
Laboratoire Inflammation, Tissus Épithéliaux et Cytokines, UPRES-EA 4331, CHU de Poitiers, Pole Biologie Santé, Université de Poitiers, Bâtiment B36, 1 rue G Bonnet, 86022 Poitiers, France univ-poitiers.fr
Search for more papers by this authorNathalie Pedretti
BIOalternatives, 1 bis rue des Plantes, 86160 Gençay, France bioalternatives.com
Search for more papers by this authorChristine Barrault
BIOalternatives, 1 bis rue des Plantes, 86160 Gençay, France bioalternatives.com
Search for more papers by this authorJulien Garnier
BIOalternatives, 1 bis rue des Plantes, 86160 Gençay, France bioalternatives.com
Search for more papers by this authorCorresponding Author
Jean-Claude Lecron
Laboratoire Inflammation, Tissus Épithéliaux et Cytokines, UPRES-EA 4331, CHU de Poitiers, Pole Biologie Santé, Université de Poitiers, Bâtiment B36, 1 rue G Bonnet, 86022 Poitiers, France univ-poitiers.fr
Search for more papers by this authorFrançois-Xavier Bernard,
Franck Morel,
Magalie Camus,
Nathalie Pedretti,
Christine Barrault,
Julien Garnier,
Jean-Claude Lecron,
François-Xavier Bernard
Laboratoire Inflammation, Tissus Épithéliaux et Cytokines, UPRES-EA 4331, CHU de Poitiers, Pole Biologie Santé, Université de Poitiers, Bâtiment B36, 1 rue G Bonnet, 86022 Poitiers, France univ-poitiers.fr
BIOalternatives, 1 bis rue des Plantes, 86160 Gençay, France bioalternatives.com
Search for more papers by this authorFranck Morel
Laboratoire Inflammation, Tissus Épithéliaux et Cytokines, UPRES-EA 4331, CHU de Poitiers, Pole Biologie Santé, Université de Poitiers, Bâtiment B36, 1 rue G Bonnet, 86022 Poitiers, France univ-poitiers.fr
Search for more papers by this authorMagalie Camus
Laboratoire Inflammation, Tissus Épithéliaux et Cytokines, UPRES-EA 4331, CHU de Poitiers, Pole Biologie Santé, Université de Poitiers, Bâtiment B36, 1 rue G Bonnet, 86022 Poitiers, France univ-poitiers.fr
Search for more papers by this authorNathalie Pedretti
BIOalternatives, 1 bis rue des Plantes, 86160 Gençay, France bioalternatives.com
Search for more papers by this authorChristine Barrault
BIOalternatives, 1 bis rue des Plantes, 86160 Gençay, France bioalternatives.com
Search for more papers by this authorJulien Garnier
BIOalternatives, 1 bis rue des Plantes, 86160 Gençay, France bioalternatives.com
Search for more papers by this authorCorresponding Author
Jean-Claude Lecron
Laboratoire Inflammation, Tissus Épithéliaux et Cytokines, UPRES-EA 4331, CHU de Poitiers, Pole Biologie Santé, Université de Poitiers, Bâtiment B36, 1 rue G Bonnet, 86022 Poitiers, France univ-poitiers.fr
Search for more papers by this authorAcademic Editor: Maria Leite-de-Moraes
Abstract
Cutaneous homeostasis and defenses are maintained by permanent cross-talk among particular epidermal keratinocytes and immune cells residing or recruited in the skin, through the production of cytokines. If required, a coordinated inflammatory response is triggered, relayed by specific cytokines. Due to numerous reasons, troubles in the resolution of this phenomenon could generate a cytokine-mediated vicious circle, promoting skin chronic inflammation, the most common being atopic dermatitis and psoriasis. In this paper, we discuss the biological effects of cytokine on keratinocytes, more particularly on specific or shared cytokines involved in atopic dermatitis or psoriasis. We report and discuss monolayer or 3D in vitro models of keratinocytes stimulated by specific sets of cytokines to mimic atopic dermatitis or psoriasis. IL-22, TNFa, IL-4, and IL-13 combination is able to mimic an “atopic dermatitis like” state. In psoriasis lesions, over expression of IL-17 is observed whereas IL-4 and IL-13 were not detected; the replacement of IL-4 and IL-13 by IL-17 from this mix is able to mimic in vitro a “psoriasis like” status on keratinocytes. We conclude that specific cytokine environment deregulation plays a central role on skin morphology and innate immunity, moving towards specific pathologies and opening the way to new therapeutic strategies.
References
- 1 Di Meglio P., Gayathri Perera K., and Nestle F. O., The multitasking organ: recent insights into skin immune function, Immunity. (2011) 35, no. 6, 857–869, https://doi.org/10.1016/j.immuni.2011.12.003.
- 2 Guttman-Yassky E., Nograles K. E., and Krueger J. G., Contrasting pathogenesis of atopic dermatitis and psoriasis-part II: immune cell subsets and therapeutic concepts, Journal of Allergy and Clinical Immunology. (2011) 127, no. 6, 1420–1432, 2-s2.0-79955622264, https://doi.org/10.1016/j.jaci.2011.01.054.
- 3 Guttman-Yassky E., Nograles K. E., and Krueger J. G., Contrasting pathogenesis of atopic dermatitis and psoriasis-part I: clinical and pathologic concepts, Journal of Allergy and Clinical Immunology. (2011) 127, no. 5, 1110–1118, 2-s2.0-79955608104, https://doi.org/10.1016/j.jaci.2011.01.053.
- 4 Palmer C. N. A., Irvine A. D., Terron-Kwiatkowski A., Zhao Y., Liao H., Lee S. P., Goudie D. R., Sandilands A., Campbell L. E., Smith F. J. D., O′Regan G. M., Watson R. M., Cecil J. E., Bale S. J., Compton J. G., DiGiovanna J. J., Fleckman P., Lewis-Jones S., Arseculeratne G., Sergeant A., Munro C. S., Houate B. E., McElreavey K., Halkjaer L. B., Bisgaard H., Mukhopadhyay S., and McLean W. H. I., Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis, Nature Genetics. (2006) 38, no. 4, 441–446, 2-s2.0-33645399288, https://doi.org/10.1038/ng1767.
- 5 Lecron J., Morel F., and Boniface K., S. Saeland, Keratinocytes as targets for cytokines in skin inflammation, Recent Advances in Skin Immunology, 2008, Kerala, Kerala, India.
- 6 Boniface K., Bernard F. X., Garcia M., Gurney A. L., Lecron J. C., and Morel F., IL-22 inhibits epidermal differentiation and induces proinflammatory gene expression and migration of human keratinocytes, Journal of Immunology. (2005) 174, no. 6, 3695–3702, 2-s2.0-14844342604.
- 7 Boniface K., Diveu C., Morel F., Pedretti N., Froger J., Ravon E., Garcia M., Venereau E., Preisser L., Guignouard E., Guillet G., Dagregorio G., Pène J., Moles J. P., Yssel H., Chevalier S., Bernard F. X., Gascan H., and Lecron J. C., Oncostatin M secreted by skin infiltrating T lymphocytes is a potent keratinocyte activator involved in skin inflammation, Journal of Immunology. (2007) 178, no. 7, 4615–4622, 2-s2.0-33947671498.
- 8 Wilson N. J., Boniface K., Chan J. R., McKenzie B. S., Blumenschein W. M., Mattson J. D., Basham B., Smith K., Chen T., Morel F., Lecron J. C., Kastelein R. A., Cua D. J., McClanahan T. K., Bowman E. P., and Malefyt R. D. W., Development, cytokine profile and function of human interleukin 17-producing helper T cells, Nature Immunology. (2007) 8, no. 9, 950–957, 2-s2.0-34548133583, https://doi.org/10.1038/ni1497.
- 9 Caruso R., Botti E., Sarra M., Esposito M., Stolfi C., Diluvio L., Giustizieri M. L., Pacciani V., Mazzotta A., Campione E., MacDonald T. T., Chimenti S., Pallone F., Costanzo A., and Monteleone G., Involvement of interleukin-21 in the epidermal hyperplasia of psoriasis, Nature Medicine. (2009) 15, no. 9, 1013–1015, 2-s2.0-69949142054, https://doi.org/10.1038/nm.1995.
- 10 Wittmann M., Purwar R., Hartmann C., Gutzmer R., and Werfel T., Human keratinocytes respond to interleukin-18: implication for the course of chronic inflammatory skin diseases, Journal of Investigative Dermatology. (2005) 124, no. 6, 1225–1233, 2-s2.0-20544448597, https://doi.org/10.1111/j.0022-202X.2005.23715.x.
- 11 Boniface K., Lecron J. C., Bernard F. X., Dagregorio G., Guillet G., Nau F., and Morel F., Keratinocytes as targets for interleukin-10-related cytokines: a putative role in the pathogenesis of psoriasis, European Cytokine Network. (2005) 16, no. 4, 309–319, 2-s2.0-33750712522.
- 12 Sa S. M., Valdez P. A., Wu J., Jung K., Zhong F., Hall L., Kasman I., Winer J., Modrusan Z., Danilenko D. M., and Ouyang W., The effects of IL-20 subfamily cytokines on reconstituted human epidermis suggest potential roles in cutaneous innate defense and pathogenic adaptive immunity in psoriasis, Journal of Immunology. (2007) 178, no. 11, 2229–2240, 2-s2.0-34249800089.
- 13 Caruso R., Botti E., Sarra M., Esposito M., Stolfi C., Diluvio L., Giustizieri M. L., Pacciani V., Mazzotta A., Campione E., MacDonald T. T., Chimenti S., Pallone F., Costanzo A., and Monteleone G., Involvement of interleukin-21 in the epidermal hyperplasia of psoriasis, Nature Medicine. (2009) 15, no. 9, 1013–1015, 2-s2.0-69949142054, https://doi.org/10.1038/nm.1995.
- 14 Guilloteau K., Paris I., Pedretti N., Boniface K., Juchaux F., Huguier V., Guillet G., Bernard F. X., Lecron J. C., and Morel F., Skin inflammation induced by the synergistic action of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α recapitulates some features of psoriasis, Journal of Immunology. (2010) 184, no. 9, 5263–5270, 2-s2.0-77955352799, https://doi.org/10.4049/jimmunol.0902464.
- 15 Carrier Y., Ma H. L., Ramon H. E., Napierata L., Small C., ′Toole M. O., Young D. A., Fouser L. A., Nickerson-Nutter C., Collins M., Dunussi-Joannopoulos K., and Medley Q. G., Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in vivo: implications in psoriasis pathogenesis, Journal of Investigative Dermatology. (2011) 131, 2428–2437, https://doi.org/10.1038/jid.2011.234.
- 16 Lebre M. C., Van Der Aar A. M. G., Van Baarsen L., Van Capel T. M. M., Schuitemaker J. H. N., Kapsenberg M. L., and De Jong E. C., Human keratinocytes express functional toll-like receptor 3, 4, 5, and 9, Journal of Investigative Dermatology. (2007) 127, no. 2, 331–341, 2-s2.0-33846240438, https://doi.org/10.1038/sj.jid.5700530.
- 17 Miller L. S., Toll-like receptors in skin, Advances in Dermatology C. (2008) 24, 71–87, 2-s2.0-56349156617, https://doi.org/10.1016/j.yadr.2008.09.004.
- 18 Kinoshita H., Takai T., Anh Le T., Kamijo S., Ling Wang X., Ushio H., Hara M., Kawasaki J., Tuan Vu A., Ogawa T., Gunawan H., Ikeda S., Okumura K., and Ogawa H., Cytokine milieu modulates release of thymic stromal lymphopoietin from human keratinocytes stimulated with double-stranded RNA, Journal of Allergy and Clinical Immunology. (2009) 123, no. 1, 179–186, 2-s2.0-58149108996, https://doi.org/10.1016/j.jaci.2008.10.008.
- 19 Nograles K. E., Zaba L. C., Guttman-Yassky E., Fuentes-Duculan J., Suárez-Fariñas M., Cardinale I., Khatcherian A., Gonzalez J., Pierson K. C., White T. R., Pensabene C., Coats I., Novitskaya I., Lowes M. A., and Krueger J. G., Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways, British Journal of Dermatology. (2008) 159, no. 5, 1092–1102, 2-s2.0-54249130813, https://doi.org/10.1111/j.1365-2133.2008.08769.x.
- 20 Teunissen M. B. M., Koomen C. W., De Waal Malefyt R., Wierenga E. A., and Bos J. D., Interleukin-17 and interferon-γ synergize in the enhancement of proinflammatory cytokine production by human keratinocytes, Journal of Investigative Dermatology. (1998) 111, no. 4, 645–649, 2-s2.0-0031691282, https://doi.org/10.1046/j.1523-1747.1998.00347.x.
- 21 Albanesi C., Cavani A., and Girolomoni G., IL-17 is produced by nickel-specific T lymphocytes and regulates ICAM-1 expression and chemokine production in human keratinocytes: synergistic or antagonist effects with IFN-γ and TNF-α, Journal of Immunology. (1999) 162, no. 1, 494–502, 2-s2.0-0032939560.
- 22 Liang S. C., Tan X. Y., Luxenberg D. P., Karim R., Dunussi-Joannopoulos K., Collins M., and Fouser L. A., Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides, Journal of Experimental Medicine. (2006) 203, no. 10, 2271–2279, 2-s2.0-33749318470, https://doi.org/10.1084/jem.20061308.
- 23 Ghannam S., Dejou C., Pedretti N., Giot J. P., Dorgham K., Boukhaddaoui H., Deleuze V., Bernard F. X., Jorgensen C., Yssel H., and Pène J., CCL20 and β-defensin-2 induce arrest of human Th17 cells on inflamed endothelium in vitro under flow conditions, Journal of Immunology. (2011) 186, no. 3, 1411–1420, 2-s2.0-79251564771, https://doi.org/10.4049/jimmunol.1000597.
- 24 Purwar R., Werfel T., and Wittmann M., IL-13-stimulated human keratinocytes preferentially attract CD4+ CCR4+ T cells: possible role in atopic dermatitis, Journal of Investigative Dermatology. (2006) 126, no. 5, 1043–1051, 2-s2.0-33646157750, https://doi.org/10.1038/sj.jid.5700085.
- 25 Albanesi C., Fairchild H. R., Madonna S., Scarponi C., De Pità O., Leung D. Y. M., and Howell M. D., IL-4 and IL-13 negatively regulate TNF-β- and IFN-γ-induced β-defensin expression through STAT-6, suppressor of cytokine signaling (SOCS)-1, and SOCS-3, Journal of Immunology. (2007) 179, no. 2, 984–992, 2-s2.0-34548721076.
- 26 Nomura I., Goleva E., Howell M. D., Hamid Q. A., Ong P. Y., Hall C. F., Darst M. A., Gao B., Boguniewicz M., Travers J. B., and Leung D. Y. M., Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes, Journal of Immunology. (2003) 171, no. 6, 3262–3269, 2-s2.0-0041331649.
- 27 Ong P. Y., Ohtake T., Brandt C., Strickland I., Boguniewicz M., Ganz T., Gallo R. L., and Leung D. Y. M., Endogenous antimicrobial peptides and skin infections in atopic dermatitis, New England Journal of Medicine. (2002) 347, no. 15, 1151–1160, 2-s2.0-0037057645, https://doi.org/10.1056/NEJMoa021481.
- 28 Bogiatzi S. I., Fernandez I., Bichet J. C., Marloie-Provost M. A., Volpe E., Sastre X., and Soumelis V., Cutting edge: proinflammatory and Th2 cytokines synergize to induce thymic stromal lymphopoietin production by human skin keratinocytes, Journal of Immunology. (2007) 178, no. 6, 3373–3377, 2-s2.0-33947244350.
- 29 David M., Ford D., Bertoglio J., Maizel A. L., and Pierre J., Induction of the IL-13 receptor α2-chain by IL-4 and IL-13 in human keratinocytes: involvement of STAT6, ERK and p38 MAPK pathways, Oncogene. (2001) 20, no. 46, 6660–6668, 2-s2.0-0035845855, https://doi.org/10.1038/sj.onc.1204629.
- 30 Wongpiyabovorn J., Suto H., Ushio H., Izuhara K., Mitsuishi K., Ikeda S., Nakao A., Okumura K., and Ogawa H., Up-regulation of interleukin-13 receptor α1 on human keratinocytes in the skin of psoriasis and atopic dermatitis, Journal of Dermatological Science. (2003) 33, no. 1, 31–40, 2-s2.0-0141535273, https://doi.org/10.1016/S0923-1811(03)00148-8.
- 31 Farrar M. A. and Schreiber R. D., The molecular cell biology of interferon-γ and its receptor, Annual Review of Immunology. (1993) 11, 571–611, 2-s2.0-0027411525.
- 32 Nomura I., Gao B., Boguniewicz M., Darst M. A., Travers J. B., and Leung D. Y. M., Distinct patterns of gene expression in the skin lesions of atopic dermatitis and psoriasis: a gene microarray analysis, Journal of Allergy and Clinical Immunology. (2003) 112, no. 6, 1195–1202, 2-s2.0-0346995201, https://doi.org/10.1016/j.jaci.2003.08.049.
- 33 Uyemura K., Yamamura M., Fivenson D. F., Modlin R. L., and Nickoloff B. J., The cytokine network in lesional and lesion-free psoriatic skin is characterized by a T-helper Type 1 cell-mediated response, Journal of Investigative Dermatology. (1993) 101, no. 5, 701–705, 2-s2.0-0027439191.
- 34 Szegedi A., Aleksza M., Gonda A., Irinyi B., Sipka S., Hunyadi J., and Antal-Szalmás P., Elevated rate of Thelper1 (TH1) lymphocytes and serum IFN-γ levels in psoriatic patients, Immunology Letters. (2003) 86, no. 3, 277–280, 2-s2.0-0037403907, https://doi.org/10.1016/S0165-2478(03)00025-7.
- 35 Austin L. M., Ozawa M., Kikuchi T., Walters I. B., and Krueger J. G., The majority of epidermal T cells in psoriasis vulgaris lesions can produce type 1 cytokines, interferon-γ, interleukin-2, and tumor necrosis factor-α, defining TC1 (cytotoxic T lymphocyte) and TH1 effector populations: a type 1 differentiation bias is also measured in circulating blood T cells in psoriatic patients, Journal of Investigative Dermatology. (1999) 113, no. 5, 752–759, 2-s2.0-0032729645, https://doi.org/10.1046/j.1523-1747.1999.00749.x.
- 36 Trepicchio W. L., Ozawa M., Walters I. B., Kikuchi T., Gilleaudeau P., Bliss J. L., Schwertschlag U., Dorner A. J., and Krueger J. G., Interleukin-11 therapy selectively downregulates type I cytokine proinflammatory pathways in psoriasis lesions, Journal of Clinical Investigation. (1999) 104, no. 11, 1527–1537, 2-s2.0-0033404492.
- 37 Wolk K., Witte E., Wallace E., Döcke W. D., Kunz S., Asadullah K., Volk H. D., Sterry W., and Sabat R., IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis, European Journal of Immunology. (2006) 36, no. 5, 1309–1323, 2-s2.0-33646552450, https://doi.org/10.1002/eji.200535503.
- 38 Grewe M., Bruijnzeel-Koomen C. A. F. M., Schöpf E., Thepen T., Langeveld-Wildschut A. G., Ruzicka T., and Krutmann J., A role for Th1 and Th2 cells in the immunopathogenesis of atopic dermatitis, Immunology Today. (1998) 19, no. 8, 359–361, 2-s2.0-0031871705, https://doi.org/10.1016/S0167-5699(98)01285-7.
- 39 Groves R. W., Mizutani H., Kieffer J. D., and Kupper T. S., Inflammatory skin disease in transgenic mice that express high levels of interleukin 1α in basal epidermis, Proceedings of the National Academy of Sciences of the United States of America. (1995) 92, no. 25, 11874–11878, 2-s2.0-0029583866, https://doi.org/10.1073/pnas.92.25.11874.
- 40 Shepherd J., Little M. C., and Nicklin M. J. H., Psoriasis-like cutaneous inflammation in mice lacking interleukin-1 receptor antagonist, Journal of Investigative Dermatology. (2004) 122, no. 3, 665–669, 2-s2.0-1842689976, https://doi.org/10.1111/j.0022-202X.2004.22305.x.
- 41 Kondo S. and Sauder D. N., Tumor necrosis factor (TNF) receptor type 1 (p55) is a main mediator for TNF-α-induced skin inflammation, European Journal of Immunology. (1997) 27, no. 7, 1713–1718, 2-s2.0-0030761597, https://doi.org/10.1002/eji.1830270718.
- 42 Harder J., Bartels J., Christophers E., and Schröder J. M., Isolation and characterization of human β-defensin-3, a novel human inducible peptide antibiotic, Journal of Biological Chemistry. (2001) 276, no. 8, 5707–5713, 2-s2.0-0035937107, https://doi.org/10.1074/jbc.M008557200.
- 43 Ettehadi P., Greaves M. W., Wallach D., Aderka D., and Camp R. D. R., Elevated tumour necrosis factor-alpha (TNF-α) biological activity in psoriatic skin lesions, Clinical and Experimental Immunology. (1994) 96, no. 1, 146–151, 2-s2.0-0028233818.
- 44 Oh C. J., Das K. M., and Gottlieb A. B., Treatment with anti-tumor necrosis factor α (TNF-α) monoclonal antibody dramatically decreases the clinical activity of psoriasis lesions, Journal of the American Academy of Dermatology. (2000) 42, no. 5, 829–830, 2-s2.0-0034023433.
- 45 Chaudhari U., Romano P., Mulcahy L. D., Dooley L. T., Baker D. G., and Gottlieb A. B., Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomised trial, The Lancet. (2001) 357, no. 9271, 1842–1847, 2-s2.0-0035832515, https://doi.org/10.1016/S0140-6736(00)04954-0.
- 46 Leonardi C. L., Powers J. L., Matheson R. T., Goffe B. S., Zitnik R., Wang A., and Gottlieb A. B., Etanercept as monotherapy in patients with psoriasis, New England Journal of Medicine. (2003) 349, no. 21, 2014–2022, 2-s2.0-0344926414, https://doi.org/10.1056/NEJMoa030409.
- 47 Jacobi A., Antoni C., Manger B., Schuler G., and Hertl M., Infliximab in the treatment of moderate to severe atopic dermatitis., Journal of the American Academy of Dermatology. (2005) 52, no. 3, 522–526, 2-s2.0-24944536778.
- 48 Koga C., Kabashima K., Shiraishi N., Kobayashi M., and Tokura Y., Possible pathogenic role of Th17 cells for atopic dermatitis, Journal of Investigative Dermatology. (2008) 128, no. 11, 2625–2630, 2-s2.0-53949103784, https://doi.org/10.1038/jid.2008.111.
- 49 Toda M., Leung D. Y. M., Molet S., Boguniewicz M., Taha R., Christodoulopoulos P., Fukuda T., Elias J. A., and Hamid Q. A., Polarized in vivo expression of IL-11 and IL-17 between acute and chronic skin lesions, Journal of Allergy and Clinical Immunology. (2003) 111, no. 4, 875–881, 2-s2.0-0242670018, https://doi.org/10.1067/mai.2003.1414.
- 50 Nograles K. E., Suárez-Fariñas M., Shemer A., Fuentes-Duculan J., Chiricozzi A., Cardinale I., Zaba L. C., Kikuchi T., Ramon M., Bergman R., Krueger J. G., and Guttman-Yassky E., Atopic dermatitis keratinocytes exhibit normal TH17 cytokine responses, Journal of Allergy and Clinical Immunology. (2010) 125, no. 3, 744–e2, 2-s2.0-77649244202, https://doi.org/10.1016/j.jaci.2009.12.934.
- 51 Chan J. R., Blumenschein W., Murphy E., Diveu C., Wiekowski M., Abbondanzo S., Lucian L., Geissler R., Brodie S., Kimball A. B., Gorman D. M., Smith K., Malefyt R. D. W., Kastelein R. A., McClanahan T. K., and Bowman E. P., IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis, Journal of Experimental Medicine. (2006) 203, no. 12, 2577–2587, 2-s2.0-33751546237, https://doi.org/10.1084/jem.20060244.
- 52 Piskin G., Sylva-Steenland R. M. R., Bos J. D., and Teunissen M. B. M., In vitro and in situ expression of IL-23 by keratinocytes in healthy skin and psoriasis lesions: enhanced expression in psoriatic skin, Journal of Immunology. (2006) 176, no. 3, 1908–1915, 2-s2.0-31144441631.
- 53 Lee E., Trepicchio W. L., Oestreicher J. L., Pittman D., Wang F., Chamian F., Dhodapkar M., and Krueger J. G., Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris, Journal of Experimental Medicine. (2004) 199, no. 1, 125–130, 2-s2.0-0347285359, https://doi.org/10.1084/jem.20030451.
- 54 Bowcock A. M. and Krueger J. G., Getting under the skin: the immunogenetics of psoriasis, Nature Reviews Immunology. (2005) 5, no. 9, 699–711, 2-s2.0-25444435193, https://doi.org/10.1038/nri1689.
- 55 Boniface K., Guignouard E., Pedretti N., Garcia M., Delwail A., Bernard F. X., Nau F., Guillet G., Dagregorio G., Yssel H., Lecron J. C., and Morel F., A role for T cell-derived interleukin 22 in psoriatic skin inflammation, Clinical and Experimental Immunology. (2007) 150, no. 3, 407–415, 2-s2.0-36048953799, https://doi.org/10.1111/j.1365-2249.2007.03511.x.
- 56 Lowes M. A., Kikuchi T., Fuentes-Duculan J., Cardinale I., Zaba L. C., Haider A. S., Bowman E. P., and Krueger J. G., Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells, Journal of Investigative Dermatology. (2008) 128, no. 5, 1207–1211, 2-s2.0-42149087160, https://doi.org/10.1038/sj.jid.5701213.
- 57 Pène J., Chevalier S., Preisser L., Véneréau E., Guilleux M. H., Ghannam S., Molès J. P., Danger Y., Ravon E., Lesaux S., Yssel H., and Gascan H., Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes, Journal of Immunology. (2008) 180, no. 11, 7423–7430, 2-s2.0-47249125726.
- 58 Gray E. E., Suzuki K., and Cyster J. G., Cutting edge: identification of a motile IL-17-producing γδ T cell population in the dermis, Journal of Immunology. (2011) 186, no. 11, 6091–6095, 2-s2.0-79958072599, https://doi.org/10.4049/jimmunol.1100427.
- 59 Cai Y., Shen X., Ding C., Qi C., Li K., Li X., Jala V. R., Zhang H. G., Wang T., Zheng J., and Yan J., Pivotal role of dermal IL-17-producing gammadelta T cells in skin inflammation, Immunity. (2011) 35, no. 4, 596–610, https://doi.org/10.1016/j.immuni.2011.08.001.
- 60 Michel M. L., Keller A. C., Paget C., Fujio M., Trottein F., Savage P. B., Wong C. H., Schneider E., Dy M., and Leite-de-Moraes M. C., Identification of an IL-17-producing NK1.1neg iNKT cell population involved in airway neutrophilia, Journal of Experimental Medicine. (2007) 204, no. 5, 995–1001, 2-s2.0-34249059942, https://doi.org/10.1084/jem.20061551.
- 61 Doisne J. M., Becourt C., Amniai L., Duarte N., Le Luduec J. B., Eberl G., and Benlagha K., Skin and peripheral lymph node invariant NKT cells are mainly retinoic acid receptor-related orphan receptor γt+and respond preferentially under inflammatory conditions, Journal of Immunology. (2009) 183, no. 3, 2142–2149, 2-s2.0-68149164473, https://doi.org/10.4049/jimmunol.0901059.
- 62 Nograles K. E., Zaba L. C., Guttman-Yassky E., Fuentes-Duculan J., Suárez-Fariñas M., Cardinale I., Khatcherian A., Gonzalez J., Pierson K. C., White T. R., Pensabene C., Coats I., Novitskaya I., Lowes M. A., and Krueger J. G., Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways, British Journal of Dermatology. (2008) 159, no. 5, 1092–1102, 2-s2.0-54249130813, https://doi.org/10.1111/j.1365-2133.2008.08769.x.
- 63 Trifari S., Kaplan C. D., Tran E. H., Crellin N. K., and Spits H., Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from TH-17, TH1 and TH2 cells, Nature Immunology. (2009) 10, no. 8, 864–871, 2-s2.0-67651171182, https://doi.org/10.1038/ni.1770.
- 64 Duhen T., Geiger R., Jarrossay D., Lanzavecchia A., and Sallusto F., Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells, Nature Immunology. (2009) 10, no. 8, 857–863, 2-s2.0-67651154105, https://doi.org/10.1038/ni.1767.
- 65 Eyerich S., Eyerich K., Pennino D., Carbone T., Nasorri F., Pallotta S., Cianfarani F., Odorisio T., Traidl-Hoffmann C., Behrendt H., Durham S. R., Schmidt-Weber C. B., and Cavani A., Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling, Journal of Clinical Investigation. (2009) 119, no. 12, 3573–3585, 2-s2.0-72849131815, https://doi.org/10.1172/JCI40202.
- 66 Nograles K. E., Zaba L. C., Shemer A., Fuentes-Duculan J., Cardinale I., Kikuchi T., Ramon M., Bergman R., Krueger J. G., and Guttman-Yassky E., IL-22-producing "T22" T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells, Journal of Allergy and Clinical Immunology. (2009) 123, no. 6, 1244–e2, 2-s2.0-67649161002, https://doi.org/10.1016/j.jaci.2009.03.041.
- 67 Fujita H., Nograles K. E., Kikuchi T., Gonzalez J., Carucci J. A., and Krueger J. G., Human Langerhans cells induce distinct IL-22-producing CD4+ T cells lacking IL-17 production, Proceedings of the National Academy of Sciences of the United States of America. (2009) 106, no. 51, 21795–21800, 2-s2.0-76049091500, https://doi.org/10.1073/pnas.0911472106.
- 68 Res P. C. M., Piskin G., de Boer O. J., van der Loos C. M., Teeling P., Bos J. D., and Teunissen M. B. M., Overrepresentation of IL-17A and IL-22 Producing CD8 T Cells in Lesional Skin Suggests Their Involvement in the pathogenesis of psoriasis, PLoS ONE. (2010) 5, no. 11, 2-s2.0-78649666553, https://doi.org/10.1371/journal.pone.0014108, e14108.
- 69 Van Belle A. B., de Heusch M., Lemaire M. M., Hendrickx E., Warnier G., Dunussi-Joannopoulos K., Fouser L. A., Renauld J. C., and Dumoutier L., IL-22 is required for imiquimod-induced psoriasiform skin inflammation in mice, Journal of Immunology. (2012) 188, no. 1, 462–469, https://doi.org/10.4049/jimmunol.1102224.
- 70 Eyerich S., Onken A. T., Weidinger S., Franke A., Nasorri F., Pennino D., Grosber M., Pfab F., Schmidt-Weber C. B., Mempel M., Hein R., Ring J., Cavani A., and Eyerich K., Mutual antagonism of T cells causing psoriasis and atopic eczema, New England Journal of Medicine. (2011) 365, no. 3, 231–238, 2-s2.0-79960578839.
- 71 Rosdy M., Bertino B., Butet V., Gibbs S., Ponec M., and Darmon M., Retinoic Acid inhibits epidermal differentiation when applied topically on the stratum corneum of epidermis formed in vitro by human keratinocytes grown on defined medium, In Vitro and Molecular Toxicology. (1997) 10, no. 1, 39–47, 2-s2.0-0030985944.
