Crosstalk between ILC2 and Gata3high Treg locally constrains adaptive type-2 immunity
Crosstalk between ILC2 and Gata3high Treg locally constrains adaptive type-2 immunity
Regulatory T cells (Tregs) control adaptive immunity and restrain type 2 inflammation in allergic disease. Interleukin-33 promotes the expansion of tissue-resident Tregs and group 2 innate lymphoid cells (ILC2s); however, how Tregs locally coordinate their function within the inflammatory niche is not understood. Here, we show that ILC2s are critical orchestrators of Treg function. Using spatial, cellular, and molecular profiling of the type 2 inflamed niche, we found that ILC2s and Tregs engage in a direct (OX40L-OX40) and chemotaxis-dependent (CCL1-CCR8) cellular dialogue that enforces the local accumulation of Gata3high Tregs, which are transcriptionally and functionally adapted to the type 2 environment. Genetic interruption of ILC2-Treg communication resulted in uncontrolled type 2 lung inflammation after allergen exposure. Mechanistically, we found that Gata3high Tregs can modulate the local bioavailability of the costimulatory molecule OX40L, which subsequently controlled effector memory T helper 2 cell numbers. Hence, ILC2-Treg interactions represent a critical feedback mechanism to control adaptive type 2 immunity.
Stockis, Julie
657f31c7-ad68-4af0-95b4-1bbad863af1e
Yip, Thomas
acec9536-bb11-47b9-8c96-4c8f8e81506b
Moreno-Vicente, Julie
7d453a38-38e8-49a5-8804-cc1dffbc981a
Cragg, Mark S.
ec97f80e-f3c8-49b7-a960-20dff648b78c
Stockis, Julie
657f31c7-ad68-4af0-95b4-1bbad863af1e
Yip, Thomas
acec9536-bb11-47b9-8c96-4c8f8e81506b
Moreno-Vicente, Julie
7d453a38-38e8-49a5-8804-cc1dffbc981a
Cragg, Mark S.
ec97f80e-f3c8-49b7-a960-20dff648b78c
Stockis, Julie, Yip, Thomas and Moreno-Vicente, Julie
,
et al.
(2024)
Crosstalk between ILC2 and Gata3high Treg locally constrains adaptive type-2 immunity.
Science immunology, 9 (97), [eadl1903].
(doi:10.1126/sciimmunol.adl1903).
Abstract
Regulatory T cells (Tregs) control adaptive immunity and restrain type 2 inflammation in allergic disease. Interleukin-33 promotes the expansion of tissue-resident Tregs and group 2 innate lymphoid cells (ILC2s); however, how Tregs locally coordinate their function within the inflammatory niche is not understood. Here, we show that ILC2s are critical orchestrators of Treg function. Using spatial, cellular, and molecular profiling of the type 2 inflamed niche, we found that ILC2s and Tregs engage in a direct (OX40L-OX40) and chemotaxis-dependent (CCL1-CCR8) cellular dialogue that enforces the local accumulation of Gata3high Tregs, which are transcriptionally and functionally adapted to the type 2 environment. Genetic interruption of ILC2-Treg communication resulted in uncontrolled type 2 lung inflammation after allergen exposure. Mechanistically, we found that Gata3high Tregs can modulate the local bioavailability of the costimulatory molecule OX40L, which subsequently controlled effector memory T helper 2 cell numbers. Hence, ILC2-Treg interactions represent a critical feedback mechanism to control adaptive type 2 immunity.
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Accepted/In Press date: 26 June 2024
e-pub ahead of print date: 19 July 2024
Identifiers
Local EPrints ID: 493254
URI: http://eprints.soton.ac.uk/id/eprint/493254
ISSN: 2470-9468
PURE UUID: 5839fc7f-7305-4e45-bca7-221dcdb5c4c7
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Date deposited: 29 Aug 2024 16:31
Last modified: 30 Aug 2024 01:35
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Author:
Julie Stockis
Author:
Thomas Yip
Author:
Julie Moreno-Vicente
Corporate Author: et al.
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