Multiple-checkpoint inhibition of thymic stromal lymphopoietin–induced TH2 response by TH17-related cytokines

The interplay between allergy and autoimmunity has been a matter of long debate. Epidemiologic studies point to a decreased frequency of allergy in patients with autoimmune diseases. However, recent studies suggest that IL-17 and related cytokines, which play a central role in autoimmunity, might al...

Full description

Saved in:
Bibliographic Details
Published in:Journal of allergy and clinical immunology 2012-07, Vol.130 (1), p.233-240.e5
Main Authors: Bogiatzi, Sofia I., Guillot-Delost, Maude, Cappuccio, Antonio, Bichet, Jean-Christophe, Chouchane-Mlik, Olfa, Donnadieu, Marie-Hélène, Barillot, Emmanuel, Hupé, Philippe, Chlichlia, Katerina, Efremidou, Eleni I., Aractingi, Selim, Bayrou, Olivier, Soumelis, Vassili
Format: Article
Language:English
Subjects:
Allergies
allergy
Asthma
Autoimmunity
Biological and medical sciences
Blood banks
Cell Differentiation
Cells, Cultured
Cytokines - antagonists & inhibitors
Cytokines - biosynthesis
Cytokines - immunology
Cytokines - metabolism
dendritic cells
Dendritic Cells - immunology
Dendritic Cells - metabolism
Dermatitis, Atopic - immunology
Dermatitis, Atopic - metabolism
Dermatitis, Atopic - physiopathology
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Humans
Immune system
Immunopathology
Interleukin-17 - metabolism
Interleukin-17 - pharmacology
Lymphocytes
Medical sciences
Multiple sclerosis
Multivariate analysis
Rheumatoid arthritis
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
Skin
Skin - immunology
Skin - metabolism
Skin - physiopathology
Studies
TH17
Th17 Cells - immunology
Th17 Cells - metabolism
Th2 Cells - cytology
Th2 Cells - drug effects
Th2 Cells - immunology
Th2 Cells - metabolism
Thymic stromal lymphopoietin
T cells
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The interplay between allergy and autoimmunity has been a matter of long debate. Epidemiologic studies point to a decreased frequency of allergy in patients with autoimmune diseases. However, recent studies suggest that IL-17 and related cytokines, which play a central role in autoimmunity, might also promote allergy. To address this controversy, we systematically studied the interactions between TH17-related cytokines and the thymic stromal lymphopoietin (TSLP)–mediated proallergic pathway. We used human primary dendritic cells (DCs), T cells, and skin explants. A novel geometric representation and multivariate ANOVA were used to analyze the TH cytokine profile. We show that IL-17A specifically inhibits TSLP production but increases proinflammatory IL-8 production in human skin explants exposed to TNF-α and IL-4. This inhibitory activity was confirmed in cultured skin explants of atopic dermatitis lesions. At the T-cell level, TH17-polarizing cytokines (IL-1β, IL-6, TGF-β, and IL-23) inhibited TH2 differentiation induced by TSLP-activated DCs. This led to a global dominance of a TH17-polarizing environment over TSLP-activated DCs, as revealed by clustering and computational analysis. Our data indicate that TH17-related cytokines are negative regulators of the TSLP immune pathway. This might explain the decreased frequency of allergy in patients with autoimmunity and suggests new means of manipulating proallergic responses.
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2012.04.038