TY - JOUR
T1 - Thymic stromal lymphopoietin links keratinocytes and dendritic cell-derived IL-23 in patients with psoriasis
AU - Volpe, Elisabetta
AU - Pattarini, Lucia
AU - Martinez-Cingolani, Carolina
AU - Meller, Stephan
AU - Donnadieu, Marie Helene
AU - Bogiatzi, Sofia I.
AU - Fernandez, Maria I.
AU - Touzot, Maxime
AU - Bichet, Jean Christophe
AU - Reyal, Fabien
AU - Paronetto, Maria Paola
AU - Chiricozzi, Andrea
AU - Chimenti, Sergio
AU - Nasorri, Francesca
AU - Cavani, Andrea
AU - Kislat, Andreas
AU - Homey, Bernhard
AU - Soumelis, Vassili
PY - 2014
Y1 - 2014
N2 - Background Thymic stromal lymphopoietin (TSLP) is a major proallergic cytokine that promotes TH2 responses through dendritic cell (DC) activation. Whether it also plays a role in human autoimmune inflammation and associated pathways is not known. Objective In this study we investigated the potential role of several epithelium-derived factors, including TSLP, in inducing IL-23 production by human DCs. We further dissected the role of TSLP in patients with psoriasis, an IL-23-associated skin autoimmune disease. Methods The study was performed in human subjects using primary cells and tissue samples from patients with psoriasis and healthy donors. We analyzed the production of IL-23 in vitro by blood and skin DCs. We studied the function for TSLP and its interaction with other components of the inflammatory microenvironment in situ and ex vivo. Results We found that TSLP synergized with CD40 ligand to promote DC activation and pathogenic IL-23 production by primary blood and skin DCs. In situ TSLP was strongly expressed by keratinocytes of untreated psoriatic lesions but not in normal skin. Moreover, we could demonstrate that IL-4, an important component of the TH2 inflammation seen in patients with atopic dermatitis, inhibited IL-23 production induced by TSLP and CD40 ligand in a signal transducer and activator of transcription 6-independent manner. Conclusion Our results identify TSLP as a novel player within the complex psoriasis cytokine network. Blocking TSLP in patients with psoriasis might contribute to decreasing DC activation and shutting down the production of pathogenic IL-23.
AB - Background Thymic stromal lymphopoietin (TSLP) is a major proallergic cytokine that promotes TH2 responses through dendritic cell (DC) activation. Whether it also plays a role in human autoimmune inflammation and associated pathways is not known. Objective In this study we investigated the potential role of several epithelium-derived factors, including TSLP, in inducing IL-23 production by human DCs. We further dissected the role of TSLP in patients with psoriasis, an IL-23-associated skin autoimmune disease. Methods The study was performed in human subjects using primary cells and tissue samples from patients with psoriasis and healthy donors. We analyzed the production of IL-23 in vitro by blood and skin DCs. We studied the function for TSLP and its interaction with other components of the inflammatory microenvironment in situ and ex vivo. Results We found that TSLP synergized with CD40 ligand to promote DC activation and pathogenic IL-23 production by primary blood and skin DCs. In situ TSLP was strongly expressed by keratinocytes of untreated psoriatic lesions but not in normal skin. Moreover, we could demonstrate that IL-4, an important component of the TH2 inflammation seen in patients with atopic dermatitis, inhibited IL-23 production induced by TSLP and CD40 ligand in a signal transducer and activator of transcription 6-independent manner. Conclusion Our results identify TSLP as a novel player within the complex psoriasis cytokine network. Blocking TSLP in patients with psoriasis might contribute to decreasing DC activation and shutting down the production of pathogenic IL-23.
KW - CD40 ligand
KW - dendritic cells
KW - IL-23
KW - psoriasis
KW - skin inflammation
KW - Thymic stromal lymphopoietin
UR - http://www.scopus.com/inward/record.url?scp=84905474658&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84905474658&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2014.04.022
DO - 10.1016/j.jaci.2014.04.022
M3 - Article
C2 - 24910175
AN - SCOPUS:84905474658
VL - 134
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 2
ER -