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ILC2s regulate adaptive Th2 cell functions via PD-L1 checkpoint control

Group 2 innate lymphoid cells (ILC2s) are important effector cells driving the initiation of type 2 immune responses leading to adaptive T helper 2 (Th2) immunity. Here we show that ILC2s dynamically express the checkpoint inhibitor molecule PD-L1 during type 2 pulmonary responses. Surprisingly, PD-...

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Autores principales: Schwartz, Christian, Khan, Adnan R., Floudas, Achilleas, Saunders, Sean P., Hams, Emily, Rodewald, Hans-Reimer, McKenzie, Andrew N.J., Fallon, Padraic G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584124/
https://www.ncbi.nlm.nih.gov/pubmed/28747424
http://dx.doi.org/10.1084/jem.20170051
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author Schwartz, Christian
Khan, Adnan R.
Floudas, Achilleas
Saunders, Sean P.
Hams, Emily
Rodewald, Hans-Reimer
McKenzie, Andrew N.J.
Fallon, Padraic G.
author_facet Schwartz, Christian
Khan, Adnan R.
Floudas, Achilleas
Saunders, Sean P.
Hams, Emily
Rodewald, Hans-Reimer
McKenzie, Andrew N.J.
Fallon, Padraic G.
author_sort Schwartz, Christian
collection PubMed
description Group 2 innate lymphoid cells (ILC2s) are important effector cells driving the initiation of type 2 immune responses leading to adaptive T helper 2 (Th2) immunity. Here we show that ILC2s dynamically express the checkpoint inhibitor molecule PD-L1 during type 2 pulmonary responses. Surprisingly, PD-L1:PD-1 interaction between ILC2s and CD4(+) T cells did not inhibit the T cell response, but PD-L1–expressing ILC2s stimulated increased expression of GATA3 and production of IL-13 by Th2 cells both in vitro and in vivo. Conditional deletion of PD-L1 on ILC2s impaired early Th2 polarization and cytokine production, leading to delayed worm expulsion during infection with the gastrointestinal helminth Nippostrongylus brasiliensis. Our results identify a novel PD-L1–controlled mechanism for type 2 polarization, with ILC2s mediating an innate checkpoint to control adaptive T helper responses, which has important implications for the treatment of type 2 inflammation.
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spelling pubmed-55841242018-03-04 ILC2s regulate adaptive Th2 cell functions via PD-L1 checkpoint control Schwartz, Christian Khan, Adnan R. Floudas, Achilleas Saunders, Sean P. Hams, Emily Rodewald, Hans-Reimer McKenzie, Andrew N.J. Fallon, Padraic G. J Exp Med Research Articles Group 2 innate lymphoid cells (ILC2s) are important effector cells driving the initiation of type 2 immune responses leading to adaptive T helper 2 (Th2) immunity. Here we show that ILC2s dynamically express the checkpoint inhibitor molecule PD-L1 during type 2 pulmonary responses. Surprisingly, PD-L1:PD-1 interaction between ILC2s and CD4(+) T cells did not inhibit the T cell response, but PD-L1–expressing ILC2s stimulated increased expression of GATA3 and production of IL-13 by Th2 cells both in vitro and in vivo. Conditional deletion of PD-L1 on ILC2s impaired early Th2 polarization and cytokine production, leading to delayed worm expulsion during infection with the gastrointestinal helminth Nippostrongylus brasiliensis. Our results identify a novel PD-L1–controlled mechanism for type 2 polarization, with ILC2s mediating an innate checkpoint to control adaptive T helper responses, which has important implications for the treatment of type 2 inflammation. The Rockefeller University Press 2017-09-04 /pmc/articles/PMC5584124/ /pubmed/28747424 http://dx.doi.org/10.1084/jem.20170051 Text en © 2017 Schwartz et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Schwartz, Christian
Khan, Adnan R.
Floudas, Achilleas
Saunders, Sean P.
Hams, Emily
Rodewald, Hans-Reimer
McKenzie, Andrew N.J.
Fallon, Padraic G.
ILC2s regulate adaptive Th2 cell functions via PD-L1 checkpoint control
title ILC2s regulate adaptive Th2 cell functions via PD-L1 checkpoint control
title_full ILC2s regulate adaptive Th2 cell functions via PD-L1 checkpoint control
title_fullStr ILC2s regulate adaptive Th2 cell functions via PD-L1 checkpoint control
title_full_unstemmed ILC2s regulate adaptive Th2 cell functions via PD-L1 checkpoint control
title_short ILC2s regulate adaptive Th2 cell functions via PD-L1 checkpoint control
title_sort ilc2s regulate adaptive th2 cell functions via pd-l1 checkpoint control
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584124/
https://www.ncbi.nlm.nih.gov/pubmed/28747424
http://dx.doi.org/10.1084/jem.20170051
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