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Intestinal IFN-γ-producing type 1 regulatory T cells coexpress CCR5 and programmed cell death protein 1 and downregulate IL-10 in the inflamed guts of patients with inflammatory bowel disease

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Intestinal IFN-γ-producing type 1 regulatory T cells coexpress CCR5 and programmed cell death protein 1 and downregulate IL-10 in the inflamed guts of patients with inflammatory bowel disease. / Alfen, Johanna Sophie; Larghi, Paola; Facciotti, Federica; Gagliani, Nicola; Bosotti, Roberto; Paroni, Moira; Maglie, Stefano; Gruarin, Paola; Vasco, Chiara Maria; Ranzani, Valeria; Frusteri, Cristina; Iseppon, Andrea; Moro, Monica; Crosti, Maria Cristina; Gatti, Stefano; Pagani, Massimiliano; Caprioli, Flavio; Abrignani, Sergio; Flavell, Richard A; Geginat, Jens.

In: J ALLERGY CLIN IMMUN, Vol. 142, No. 5, 11.2018, p. 1537-1547.e8.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Alfen, JS, Larghi, P, Facciotti, F, Gagliani, N, Bosotti, R, Paroni, M, Maglie, S, Gruarin, P, Vasco, CM, Ranzani, V, Frusteri, C, Iseppon, A, Moro, M, Crosti, MC, Gatti, S, Pagani, M, Caprioli, F, Abrignani, S, Flavell, RA & Geginat, J 2018, 'Intestinal IFN-γ-producing type 1 regulatory T cells coexpress CCR5 and programmed cell death protein 1 and downregulate IL-10 in the inflamed guts of patients with inflammatory bowel disease', J ALLERGY CLIN IMMUN, vol. 142, no. 5, pp. 1537-1547.e8. https://doi.org/10.1016/j.jaci.2017.12.984

APA

Alfen, J. S., Larghi, P., Facciotti, F., Gagliani, N., Bosotti, R., Paroni, M., Maglie, S., Gruarin, P., Vasco, C. M., Ranzani, V., Frusteri, C., Iseppon, A., Moro, M., Crosti, M. C., Gatti, S., Pagani, M., Caprioli, F., Abrignani, S., Flavell, R. A., & Geginat, J. (2018). Intestinal IFN-γ-producing type 1 regulatory T cells coexpress CCR5 and programmed cell death protein 1 and downregulate IL-10 in the inflamed guts of patients with inflammatory bowel disease. J ALLERGY CLIN IMMUN, 142(5), 1537-1547.e8. https://doi.org/10.1016/j.jaci.2017.12.984

Vancouver

Alfen JS, Larghi P, Facciotti F, Gagliani N, Bosotti R, Paroni M et al. Intestinal IFN-γ-producing type 1 regulatory T cells coexpress CCR5 and programmed cell death protein 1 and downregulate IL-10 in the inflamed guts of patients with inflammatory bowel disease. J ALLERGY CLIN IMMUN. 2018 Nov;142(5):1537-1547.e8. https://doi.org/10.1016/j.jaci.2017.12.984

Bibtex

@article{c78c535e1c124ef38715a32fcc0af906,
title = "Intestinal IFN-γ-producing type 1 regulatory T cells coexpress CCR5 and programmed cell death protein 1 and downregulate IL-10 in the inflamed guts of patients with inflammatory bowel disease",
abstract = "BACKGROUND: IL-10 is an anti-inflammatory cytokine required for intestinal immune homeostasis. It mediates suppression of T-cell responses by type 1 regulatory T (TR1) cells but is also produced by CD25+ regulatory T (Treg) cells.OBJECTIVE: We aimed to identify and characterize human intestinal TR1 cells and to investigate whether they are a relevant cellular source of IL-10 in patients with inflammatory bowel diseases (IBDs).METHODS: CD4+ T cells isolated from the intestinal lamina propria of human subjects and mice were analyzed for phenotype, cytokine production, and suppressive capacities. Intracellular IL-10 expression by CD4+ T-cell subsets in the inflamed guts of patients with IBD (Crohn disease or ulcerative colitis) was compared with that in cells from noninflamed control subjects. Finally, the effects of proinflammatory cytokines on T-cell IL-10 expression were analyzed, and IL-1β and IL-23 responsiveness was assessed.RESULTS: Intestinal TR1 cells could be identified by coexpression of CCR5 and programmed cell death protein 1 (PD-1) in human subjects and mice. CCR5+PD-1+ TR1 cells expressed IFN-γ and efficiently suppressed T-cell proliferation and transfer colitis. Intestinal IFN-γ+ TR1 cells, but not IL-7 receptor-positive TH cells or CD25+ Treg cells, showed lower IL-10 expression in patients with IBDs. TR1 cells were responsive to IL-23, and IFN-γ+ TR1 cells downregulated IL-10 with IL-1β and IL-23. Conversely, CD25+ Treg cells expressed higher levels of IL-1 receptor but showed stable IL-10 expression.CONCLUSIONS: We provide the first ex vivo characterization of human intestinal TR1 cells. Selective downregulation of IL-10 by IFN-γ+ TR1 cells in response to proinflammatory cytokines is likely to drive excessive intestinal inflammation in patients with IBDs.",
keywords = "Journal Article",
author = "Alfen, {Johanna Sophie} and Paola Larghi and Federica Facciotti and Nicola Gagliani and Roberto Bosotti and Moira Paroni and Stefano Maglie and Paola Gruarin and Vasco, {Chiara Maria} and Valeria Ranzani and Cristina Frusteri and Andrea Iseppon and Monica Moro and Crosti, {Maria Cristina} and Stefano Gatti and Massimiliano Pagani and Flavio Caprioli and Sergio Abrignani and Flavell, {Richard A} and Jens Geginat",
note = "Copyright {\textcopyright} 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.",
year = "2018",
month = nov,
doi = "10.1016/j.jaci.2017.12.984",
language = "English",
volume = "142",
pages = "1537--1547.e8",
journal = "J ALLERGY CLIN IMMUN",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "5",

}

RIS

TY - JOUR

T1 - Intestinal IFN-γ-producing type 1 regulatory T cells coexpress CCR5 and programmed cell death protein 1 and downregulate IL-10 in the inflamed guts of patients with inflammatory bowel disease

AU - Alfen, Johanna Sophie

AU - Larghi, Paola

AU - Facciotti, Federica

AU - Gagliani, Nicola

AU - Bosotti, Roberto

AU - Paroni, Moira

AU - Maglie, Stefano

AU - Gruarin, Paola

AU - Vasco, Chiara Maria

AU - Ranzani, Valeria

AU - Frusteri, Cristina

AU - Iseppon, Andrea

AU - Moro, Monica

AU - Crosti, Maria Cristina

AU - Gatti, Stefano

AU - Pagani, Massimiliano

AU - Caprioli, Flavio

AU - Abrignani, Sergio

AU - Flavell, Richard A

AU - Geginat, Jens

N1 - Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

PY - 2018/11

Y1 - 2018/11

N2 - BACKGROUND: IL-10 is an anti-inflammatory cytokine required for intestinal immune homeostasis. It mediates suppression of T-cell responses by type 1 regulatory T (TR1) cells but is also produced by CD25+ regulatory T (Treg) cells.OBJECTIVE: We aimed to identify and characterize human intestinal TR1 cells and to investigate whether they are a relevant cellular source of IL-10 in patients with inflammatory bowel diseases (IBDs).METHODS: CD4+ T cells isolated from the intestinal lamina propria of human subjects and mice were analyzed for phenotype, cytokine production, and suppressive capacities. Intracellular IL-10 expression by CD4+ T-cell subsets in the inflamed guts of patients with IBD (Crohn disease or ulcerative colitis) was compared with that in cells from noninflamed control subjects. Finally, the effects of proinflammatory cytokines on T-cell IL-10 expression were analyzed, and IL-1β and IL-23 responsiveness was assessed.RESULTS: Intestinal TR1 cells could be identified by coexpression of CCR5 and programmed cell death protein 1 (PD-1) in human subjects and mice. CCR5+PD-1+ TR1 cells expressed IFN-γ and efficiently suppressed T-cell proliferation and transfer colitis. Intestinal IFN-γ+ TR1 cells, but not IL-7 receptor-positive TH cells or CD25+ Treg cells, showed lower IL-10 expression in patients with IBDs. TR1 cells were responsive to IL-23, and IFN-γ+ TR1 cells downregulated IL-10 with IL-1β and IL-23. Conversely, CD25+ Treg cells expressed higher levels of IL-1 receptor but showed stable IL-10 expression.CONCLUSIONS: We provide the first ex vivo characterization of human intestinal TR1 cells. Selective downregulation of IL-10 by IFN-γ+ TR1 cells in response to proinflammatory cytokines is likely to drive excessive intestinal inflammation in patients with IBDs.

AB - BACKGROUND: IL-10 is an anti-inflammatory cytokine required for intestinal immune homeostasis. It mediates suppression of T-cell responses by type 1 regulatory T (TR1) cells but is also produced by CD25+ regulatory T (Treg) cells.OBJECTIVE: We aimed to identify and characterize human intestinal TR1 cells and to investigate whether they are a relevant cellular source of IL-10 in patients with inflammatory bowel diseases (IBDs).METHODS: CD4+ T cells isolated from the intestinal lamina propria of human subjects and mice were analyzed for phenotype, cytokine production, and suppressive capacities. Intracellular IL-10 expression by CD4+ T-cell subsets in the inflamed guts of patients with IBD (Crohn disease or ulcerative colitis) was compared with that in cells from noninflamed control subjects. Finally, the effects of proinflammatory cytokines on T-cell IL-10 expression were analyzed, and IL-1β and IL-23 responsiveness was assessed.RESULTS: Intestinal TR1 cells could be identified by coexpression of CCR5 and programmed cell death protein 1 (PD-1) in human subjects and mice. CCR5+PD-1+ TR1 cells expressed IFN-γ and efficiently suppressed T-cell proliferation and transfer colitis. Intestinal IFN-γ+ TR1 cells, but not IL-7 receptor-positive TH cells or CD25+ Treg cells, showed lower IL-10 expression in patients with IBDs. TR1 cells were responsive to IL-23, and IFN-γ+ TR1 cells downregulated IL-10 with IL-1β and IL-23. Conversely, CD25+ Treg cells expressed higher levels of IL-1 receptor but showed stable IL-10 expression.CONCLUSIONS: We provide the first ex vivo characterization of human intestinal TR1 cells. Selective downregulation of IL-10 by IFN-γ+ TR1 cells in response to proinflammatory cytokines is likely to drive excessive intestinal inflammation in patients with IBDs.

KW - Journal Article

U2 - 10.1016/j.jaci.2017.12.984

DO - 10.1016/j.jaci.2017.12.984

M3 - SCORING: Journal article

C2 - 29369775

VL - 142

SP - 1537-1547.e8

JO - J ALLERGY CLIN IMMUN

JF - J ALLERGY CLIN IMMUN

SN - 0091-6749

IS - 5

ER -