Rhinovirus infection interferes with induction of tolerance to aeroantigens through OX40 ligand, thymic stromal lymphopoietin, and IL-33 - 07/01/16
Abstract |
Background |
Rhinovirus infection at an early age has been associated with development of asthma, but how rhinovirus influences the immune response is not clear.
Objective |
Tolerance to inhaled antigen is mediated through induction of regulatory T (Treg) cells, and we examined whether rhinovirus infection of the respiratory tract can block airway tolerance by modulating Treg cells.
Methods |
The immune response to intranasal ovalbumin in mice was assessed with concomitant infection with RV1B, and the factors induced in vivo were compared with those made by human lung epithelial cells infected in vitro with RV16.
Results |
RV1B infection of mice abrogated tolerance induced by inhalation of soluble ovalbumin, suppressing the normal generation of forkhead box protein 3–positive Treg cells while promoting TH2 cells. Furthermore, RV1B infection led to susceptibility to asthmatic lung disease when mice subsequently re-encountered aeroantigen. RV1B promoted early in vivo expression of the TNF family protein OX40 ligand on lung dendritic cells that was dependent on the innate cytokine thymic stromal lymphopoietin (TSLP) and also induced another innate cytokine, IL-33. Inhibiting each of these pathways allowed the natural development of Treg cells while minimizing TH2 differentiation and restored tolerance in the face of RV1B infection. In accordance, RV16 infection of human lung epithelial cells upregulated TSLP and IL-33 expression.
Conclusions |
These results suggest that infection of the respiratory epithelium with rhinovirus can antagonize tolerance to inhaled antigen through combined induction of TSLP, IL-33, and OX40 ligand and that this can lead to susceptibility to asthmatic lung inflammation.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, epithelial cell, OX40 ligand, RV1B, RV16, thymic stromal lymphopoietin, peripherally induced regulatory T cell
Abbreviations used : APC, BAL, BALF, DC, Foxp3, GAPDH, HDM, IL-33R, LDLR, LN, NHBE, OVA, OX40L, PBEC, PFU, pTreg, TCR, TLR, Treg, TSLP, TSLPR
Plan
Supported by National Institutes of Health grants AI070535 and AI103021 (to M.C.). |
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Disclosure of potential conflict of interest: A. K. Mehta, A. M. Doerner, D. H. Broide, B. L. Zuraw, and M. Croft have received research support from the National Institutes of Health. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 137 - N° 1
P. 278 - janvier 2016 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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