Annual International Days
On the occasion of World Eczema and Atopic Dermatitis Day, Iwould like to highlight some of our publications in which we investigated themechanisms underlying eczema.Our studies from 2000–2001 demonstrated the central role ofinteractions between T lymphocytes and keratinocytes in the development ofeczema in atopic dermatitis (AD) and allergic contact dermatitis. In the samework, we also developed an artificial skin model for the first time.In the basic model, activated memory/effector T cells thatselectively migrate to the skin contribute to both the initiation andmaintenance of the inflammatory response. These cells, particularly through thesecretion of IFN-γ, increase Fas receptor (FasR) expression on keratinocytes.Fas/FasL interaction subsequently induces caspase-dependent keratinocyteapoptosis, leading to disruption of epidermal barrier integrity.The experimental study published in 2000 demonstrated thateither direct contact with T cells or T-cell-derived factors could triggerkeratinocyte apoptosis, and that this process could be inhibited by Fasblockade and caspase inhibitors. Thus, keratinocyte death was defined notsimply as a consequence of inflammation, but as an active pathogenic step inthe development of eczema. (JCI)In our 2001 studies, this model was further expanded.Prolonged survival of T cells in the skin, IL-5-mediated maintenance ofeosinophils, and particularly IL-13-supported IgE responses were shown tocontribute to the persistence of chronic inflammation.In addition, we demonstrated that differential effects onintercellular adhesion proteins in keratinocytes, particularly cadherins,during T-cell-induced apoptosis may help explain the development of epidermalspongiosis.Taken together, eczema was described as a dynamic process inwhich T-cell activation, cytokine networks, Fas-mediated keratinocyteapoptosis, and disruption of epidermal cell–cell junctions mutually reinforceone another. (PubMed) In brief, the mechanism:T-hücresi aktivasyonu → deriye göç → IFN-γ ↑ → keratinositFas ↑ → Fas/FasL → kaspaz aktivasyonu → keratinosit apoptozu → epidermalbariyer bozulması + spongiozis → ekzema. Daha sonraki makalelerde TNF, TRAİL, IFN-g, TWEAK yolaklarının daetkisini ve benzer mekanizmanın astımda ve kronik sinuzitte de bariyeribozduğunu göstermistik.T cell-mediated Fas-induced keratinocyteapoptosis plays a key pathogenetic role in eczematous dermatitis. TrautmannA, Akdis M, Kleemann D, Altznauer F, Simon HU, Graeve T, Noll M, Bröcker EB,Blaser K, Akdis CA. J Clin Invest. 2000 Jul;106(1):25-35. 10.1172/JCI9199. PMID: 10880045 Free PMCarticle. https://doi.org/10.1172/JCI9199· Immune regulation in atopic dermatitis. AkdisCA, Akdis M, Trautmann A, Blaser K. Curr Opin Immunol. 2000 Dec;12(6):641-6. 10.1016/s0952-7915(00)00156-4. PMID: 11102766Review. https://doi.org/10.1016/S0952-7915(00)00156-4· Cytokine network and dysregulated apoptosisin atopic dermatitis. Akdis M, Trautmann A, Klunker S, Blaser K, Akdis CA.Acta Odontol Scand. 2001 Jun;59(3):178-82. 10.1080/000163501750266783. PMID: 11501888Review. https://doi.org/10.1080/000163501750266783· [How does eczema arise?]. Trautmann A,Disch R, Bröcker EB, Akdis CA, Gillitzer R. J Dtsch Dermatol Ges. 2003Jan;1(1):8-11. 10.1046/j.1610-0387.2003.t01-1-02020.x. PMID:16285287 Review. German. https://doi.org/10.1046/j.1610-0387.2003.t01-1-02020.x· A second step of chemotaxis aftertransendothelial migration: keratinocytes undergoing apoptosis releaseIFN-gamma-inducible protein 10, monokine induced by IFN-gamma, andIFN-gamma-inducible alpha-chemoattractant for T cell chemotaxis towardepidermis in atopic dermatitis. Klunker S, Trautmann A, Akdis M, VerhagenJ, Schmid-Grendelmeier P, Blaser K, Akdis CA. J Immunol. 2003 Jul15;171(2):1078-84. 10.4049/jimmunol.171.2.1078. PMID: 12847282. https://doi.org/10.4049/jimmunol.171.2.1078· The differential fate of cadherins duringT-cell-induced keratinocyte apoptosis leads to spongiosis in eczematousdermatitis. Trautmann A, Altznauer F, Akdis M, Simon HU, Disch R, BröckerEB, Blaser K, Akdis CA. J Invest Dermatol. 2001 Oct;117(4):927-34. 10.1046/j.0022-202x.2001.01474.x. PMID:11676834 Free article. https://doi.org/10.1046/j.0022-202x.2001.01474.x· Dual nature of T cell-epithelium interactionin chronic rhinosinusitis. Tomasz M Basinski, David Holzmann, ThomasEiwegger, Maya Zimmermann, Sven Klunker, Norbert Meyer, PeterSchmid-Grendelmeier, Marek Jutel, Cezmi A Akdis. J Allergy Clin Immunol. 2009Jul;124(1):74-80.e1-8. 10.1016/j.jaci.2009.04.019. https://doi.org/10.1016/j.jaci.2009.04.019
