Thymic stromal lymphopoietin converts human epidermal Langerhans cells into antigen-presenting cells that induce proallergic T cells.
BACKGROUND
Thymic stromal lymphopoietin (TSLP) endows human CD11c(+) dendritic cells (DCs) from peripheral blood with the capacity to induce proallergic T cells. TSLP is present at high levels in the epidermis of atopic dermatitis where it appears to trigger emigration of epidermal Langerhans cells (LCs); however, nothing else is known about the influence of TSLP on LCs.


OBJECTIVE
Effects of TSLP on human epidermal LCs were investigated.


METHODS
LCs were isolated by trypsinization from healthy human skin, highly enriched by immunomagnetic techniques (via CD1a) and cultured for 2 days. Additionally, migratory LCs were obtained by emigration from epidermal sheets for 3 days.


RESULTS
The addition of TSLP promoted survival and maturation of LCs obtained by trypsinization, as indicated by their increased expression of CD83, CD86, and high levels of MHC II. TSLP markedly increased numbers of migratory LCs. Allogeneic naïve CD4(+) T cells, cocultured with migratory TSLP-LCs produced less IFN-gamma and IL-10 and more IL-4, IL-5, IL-13, and TNF-alpha. Finally, TSLP-LCs secreted markedly more of the T(H)2 T-cell-attracting chemokine CCL17/thymus and activation-regulated chemokine.


CONCLUSIONS
These cytokine patterns correspond to those described for TSLP-treated blood DCs. They highlight a direct effect of TSLP on epidermal LCs.


CONCLUSIONS
Our data emphasize a critical role for LCs in the triggering of atopic dermatitis. Furthermore, they underscore the interest in TSLP as a potential therapeutic target in atopic diseases.
Ebner
Susanne
S
Department of Dermatology and Venereology, Kompetenzzentrum Medizin Tirol, Innsbruck, Austria.
Nguyen
Van Anh
VA
Forstner
Markus
M
Wang
Yui-Hsi
YH
Wolfram
Dolores
D
Liu
Yong-Jun
YJ
Romani
Nikolaus
N
D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D002469:Cell Separation; D002470:Cell Survival / Q000276:immunology; D016207:Cytokines / Q000502:physiology*; D003876:Dermatitis, Atopic / Q000276:immunology / Q000473:pathology; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000473:pathology; D018836:Inflammation Mediators / Q000502:physiology; D015851:Interleukin-7 / Q000502:physiology; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D046509:Tissue Culture Techniques; D015854:Up-Regulation / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D018836:Inflammation Mediators; D015851:Interleukin-7; D000094632:Thymic Stromal Lymphopoietin