Article

Thymic stromal lymphopoietin converts human epidermal Langerhans cells into antigen-presenting cells that induce proallergic T cells.

Department of Dermatology and Venereology, Kompetenzzentrum Medizin Tirol, Innsbruck, Austria.
Journal of Allergy and Clinical Immunology (impact factor: 11). 05/2007; 119(4):982-90. DOI:10.1016/j.jaci.2007.01.003 pp.982-90
Source: PubMed

ABSTRACT 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.
Effects of TSLP on human epidermal LCs were investigated.
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.
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.
These cytokine patterns correspond to those described for TSLP-treated blood DCs. They highlight a direct effect of TSLP on epidermal LCs.
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.

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Keywords

2 days
 
3 days
 
activation-regulated chemokine
 
atopic dermatitis
 
atopic diseases
 
cytokine patterns correspond
 
epidermal Langerhans cells
 
epidermal sheets
 
healthy human skin
 
human epidermal LCs
 
immunomagnetic techniques
 
increased expression
 
induce proallergic T cells
 
migratory TSLP-LCs
 
potential therapeutic target
 
T(H)2 T-cell-attracting chemokine CCL17/thymus
 
Thymic stromal lymphopoietin
 
TNF-alpha
 
TSLP-LCs secreted
 
TSLP-treated blood DCs