Staphylococcal enterotoxin A–activated regulatory T cells promote allergen-specific TH2 response to intratracheal allergen inoculation - 18/04/17
, Margaret M. McFarland, MS a, Baohua Zhou, PhD d, Silva Holtfreter, Dr rer nat e, Susan Flesher, MD b, Ambrose Cheung, MD f, Avishek Mallick, PhD gAbstract |
Background |
TH2 responses are implicated in asthma pathobiology. Epidemiologic studies have found a positive association between asthma and exposure to staphylococcal enterotoxins.
Objective |
We used a mouse model of asthma to determine whether staphylococcal enterotoxins promote TH2 differentiation of allergen-specific CD4 conventional T (Tcon) cells and asthma by activating allergen-nonspecific regulatory T (Treg) cells to create a TH2-polarizing cytokine milieu.
Methods |
Ovalbumin (OVA)–specific, staphylococcal enterotoxin A (SEA)–nonreactive naive CD4 Tcon cells were cocultured with SEA-reactive allergen-nonspecific Treg or CD4 Tcon cells in the presence of OVA and SEA. The OVA-specific CD4 T cells were then analyzed for IL-13 and IFN-γ expression. SEA-activated Treg cells were analyzed for the expression of the TH2-polarizing cytokine IL-4 and the T-cell activation markers CD69 and CD62L. For asthma induction, mice were intratracheally sensitized with OVA or cat dander extract (CDE) alone or together with SEA and then challenged with OVA or CDE. Mice were also subject to transient Treg cell depletion before sensitization with OVA plus SEA. Asthma features and TH2 differentiation in these mice were analyzed.
Results |
SEA-activated Treg cells induced IL-13 but suppressed IFN-γ expression in OVA-specific CD4 Tcon cells. SEA-activated Treg cells expressed IL-4, upregulated CD69, and downregulated CD62L. Sensitization with OVA plus SEA but not OVA alone induced asthma, and SEA exacerbated asthma induced by CDE. Depletion of Treg cells abolished these effects of SEA and IL-13 expression in OVA-specific T cells.
Conclusion |
SEA promoted TH2 responses of allergen-specific T cells and asthma pathogenesis by activating Treg cells.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, staphylococcal enterotoxin, TH2 cells, regulatory T cells
Abbreviations used : AHR, APC, BALF, CDE, DT, DTR, Foxp3, GFP, H&E, MLN, OVA, PAS, SE, SEA, Tcon, Treg
Plan
| W.-p.Z. received an AAI Travel for Technique award for this project. B.Z. was supported by R01 AI085046. |
|
| Disclosure of potential conflict of interest: B. Zhou receives research support from the National Institutes of Health. S. Holtfreter receives research support from DFG GRK1870, project C3. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 139 - N° 2
P. 508 - février 2017 Retour au numéro
Article précédent
- Early life rhinovirus wheezing, allergic sensitization, and asthma risk at adolescence
- Frederick J. Rubner, Daniel J. Jackson, Michael D. Evans, Ronald E. Gangnon, Christopher J. Tisler, Tressa E. Pappas, James E. Gern, Robert F. Lemanske
- MicroRNA-21 drives severe, steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinase–mediated suppression of histone deacetylase 2
- Richard Y. Kim, Jay C. Horvat, James W. Pinkerton, Malcolm R. Starkey, Ama T. Essilfie, Jemma R. Mayall, Prema M. Nair, Nicole G. Hansbro, Bernadette Jones, Tatt Jhong Haw, Krishna P. Sunkara, Thi Hiep Nguyen, Andrew G. Jarnicki, Simon Keely, Joerg Mattes, Ian M. Adcock, Paul S. Foster, Philip M. Hansbro
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?