King's College London

Research portal

High-Dose IL-2 Skews a Glucocorticoid-Driven IL-17+IL-10+ Memory CD4+ T Cell Response towards a Single IL-10–Producing Phenotype

Research output: Contribution to journalArticle

Standard

High-Dose IL-2 Skews a Glucocorticoid-Driven IL-17+IL-10+ Memory CD4+ T Cell Response towards a Single IL-10–Producing Phenotype. / Mann, Elizabeth H.; Gabryšová, Leona; Pfeffer, Paul E.; O’Garra, Anne; Hawrylowicz, Catherine M.

In: The Journal of Immunology, Vol. 202, No. 3, ji1800697, 01.02.2019, p. 684-693.

Research output: Contribution to journalArticle

Harvard

Mann, EH, Gabryšová, L, Pfeffer, PE, O’Garra, A & Hawrylowicz, CM 2019, 'High-Dose IL-2 Skews a Glucocorticoid-Driven IL-17+IL-10+ Memory CD4+ T Cell Response towards a Single IL-10–Producing Phenotype', The Journal of Immunology, vol. 202, no. 3, ji1800697, pp. 684-693. https://doi.org/10.4049/jimmunol.1800697

APA

Mann, E. H., Gabryšová, L., Pfeffer, P. E., O’Garra, A., & Hawrylowicz, C. M. (2019). High-Dose IL-2 Skews a Glucocorticoid-Driven IL-17+IL-10+ Memory CD4+ T Cell Response towards a Single IL-10–Producing Phenotype. The Journal of Immunology, 202(3), 684-693. [ji1800697]. https://doi.org/10.4049/jimmunol.1800697

Vancouver

Mann EH, Gabryšová L, Pfeffer PE, O’Garra A, Hawrylowicz CM. High-Dose IL-2 Skews a Glucocorticoid-Driven IL-17+IL-10+ Memory CD4+ T Cell Response towards a Single IL-10–Producing Phenotype. The Journal of Immunology. 2019 Feb 1;202(3):684-693. ji1800697. https://doi.org/10.4049/jimmunol.1800697

Author

Mann, Elizabeth H. ; Gabryšová, Leona ; Pfeffer, Paul E. ; O’Garra, Anne ; Hawrylowicz, Catherine M. / High-Dose IL-2 Skews a Glucocorticoid-Driven IL-17+IL-10+ Memory CD4+ T Cell Response towards a Single IL-10–Producing Phenotype. In: The Journal of Immunology. 2019 ; Vol. 202, No. 3. pp. 684-693.

Bibtex Download

@article{89b100fbba644dcfb75f266b2ac8750c,
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",
abstract = "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.",
author = "Mann, {Elizabeth H.} and Leona Gabryšov{\'a} and Pfeffer, {Paul E.} and Anne O’Garra and Hawrylowicz, {Catherine M.}",
year = "2019",
month = "2",
day = "1",
doi = "10.4049/jimmunol.1800697",
language = "English",
volume = "202",
pages = "684--693",
journal = "The Journal of Immunology",
publisher = "Dartmouth Publishing Co. Ltd",
number = "3",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - High-Dose IL-2 Skews a Glucocorticoid-Driven IL-17+IL-10+ Memory CD4+ T Cell Response towards a Single IL-10–Producing Phenotype

AU - Mann, Elizabeth H.

AU - Gabryšová, Leona

AU - Pfeffer, Paul E.

AU - O’Garra, Anne

AU - Hawrylowicz, Catherine M.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=85060305347&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1800697

DO - 10.4049/jimmunol.1800697

M3 - Article

VL - 202

SP - 684

EP - 693

JO - The Journal of Immunology

T2 - The Journal of Immunology

JF - The Journal of Immunology

IS - 3

M1 - ji1800697

ER -

View graph of relations

© 2018 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454