Imperial College London
Portrait Picture

ProfessorAnneO'Garra

Faculty of Medicine, National Heart & Lung Institute

Chair in Infection Immunology
 
 
 
//

Contact

 

a.ogarra

 
 
//

Location

 

Norfolk PlaceSt Mary's Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Mann:2018:10.4049/jimmunol.1800697,
author = {Mann, EH and Gabryová, L and Pfeffer, PE and O'Garra, A and Hawrylowicz, CM},
doi = {10.4049/jimmunol.1800697},
journal = {Journal of Immunology},
pages = {684--693},
title = {High-dose IL-2 skews a glucocorticoid-driven IL-17+IL-10+ memory CD4+ T cell response towards a single IL-10-producing phenotype},
url = {http://dx.doi.org/10.4049/jimmunol.1800697},
volume = {202},
year = {2018}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Glucocorticoids are known to increase production of the anti-inflammatory cytokine IL-10, and this action is associated with their clinical efficacy in asthmatics. However, glucocorticoids also enhance the synthesis of IL-17A by PBMCs, which, in excess, is associated with increased asthma severity and glucocorticoid-refractory disease. In this study, we show that the glucocorticoid dexamethasone significantly increased IL-10 production by human memory CD4+ T cells from healthy donors, as assessed by intracellular cytokine staining. In addition, dexamethasone increased production of IL-17A, IL-17F, and IL-22, with the most striking enhancement in cells coproducing Th17-associated cytokines together with IL-10. Of note, an increase in IFN-γ+IL-10+ cells was also observed despite overall downregulation of IFN-γ production. These dexamethasone-driven IL-10+ cells, and predominantly the IL-17+IL-10+ double-producing cells, were markedly refractory to the inhibitory effect of dexamethasone on proliferation and IL-2Rα expression, which facilitated their preferential IL-2-dependent expansion. Although lower concentrations of exogenous IL-2 promoted IL-10+ cells coproducing proinflammatory cytokines, higher IL-2 doses, both alone and in combination with dexamethasone, increased the proportion of single IL-10+ T cells. Thus, glucocorticoid-induced IL-10 is only accompanied by an increase of IL-17 in a low IL-2 setting, which is, nevertheless, likely to be protective owing to the induction of regulatory IL-17+IL-10+-coproducing cells. These findings open new avenues of investigation with respect to the role of IL-2 in glucocorticoid responsiveness that have potential implications for optimizing the benefit/risk ratio of glucocorticoids in the clinic.
AU  - Mann,EH
AU  - Gabryová,L
AU  - Pfeffer,PE
AU  - O'Garra,A
AU  - Hawrylowicz,CM
DO  - 10.4049/jimmunol.1800697
EP  - 693
PY  - 2018///
SN  - 1550-6606
SP  - 684
TI  - High-dose IL-2 skews a glucocorticoid-driven IL-17+IL-10+ memory CD4+ T cell response towards a single IL-10-producing phenotype
T2  - Journal of Immunology
UR  - http://dx.doi.org/10.4049/jimmunol.1800697
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30598515
UR  - http://hdl.handle.net/10044/1/66150
VL  - 202
ER  -
Download