Cross-talk between ILC2 and Gata3high Tregs locally constrains adaptive type 2 immunity

Julie Stockis; Thomas Yip; Julia Moreno-Vicente; Oliver Burton; Youhani Samarakoon; Martijn j. Schuijs; Shwetha Raghunathan; Celine Garcia; Weike Luo; Sarah k. Whiteside; Shaun Png; Charlotte Simpson; Stela Monk; Ashley Sawle; Kelvin Yin; Johanna Barbieri; Panagiotis Papadopoulos; Hannah Wong; Hans-Reimer Rodewald; Timothy Vyse; Andrew n. j. Mckenzie; Mark s. Cragg; Matthew Hoare; David r. Withers; Hans jörg Fehling; Rahul Roychoudhuri; Adrian Liston; Timotheus y. f. Halim

doi:10.1126/sciimmunol.adl1903

Cross-talk between ILC2 and Gata3^high T_regs locally constrains adaptive type 2 immunity

Julie Stockis, Thomas Yip, Julia Moreno-Vicente, Oliver Burton, Youhani Samarakoon, Martijn j. Schuijs, Shwetha Raghunathan, Celine Garcia, Weike Luo, Sarah k. Whiteside, Shaun Png, Charlotte Simpson, Stela Monk, Ashley Sawle, Kelvin Yin, Johanna Barbieri, Panagiotis Papadopoulos, Hannah Wong, Hans-Reimer Rodewald, Timothy VyseAndrew n. j. Mckenzie, Mark s. Cragg, Matthew Hoare, David r. Withers, Hans jörg Fehling, Rahul Roychoudhuri, Adrian Liston, Timotheus y. f. Halim

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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.

Original language	English
Article number	eadl1903
Journal	Science Immunology
Volume	9
Issue number	97
DOIs	https://doi.org/10.1126/sciimmunol.adl1903
Publication status	Published - 19 Jul 2024

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Manuscript - Stockis et al. (19 Aug 2023)Accepted author manuscript, 2.01 MB

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Stockis, J., Yip, T., Moreno-Vicente, J., Burton, O., Samarakoon, Y., Schuijs, M. J., Raghunathan, S., Garcia, C., Luo, W., Whiteside, S. K., Png, S., Simpson, C., Monk, S., Sawle, A., Yin, K., Barbieri, J., Papadopoulos, P., Wong, H., Rodewald, H.-R., ... Halim, T. Y. F. (2024). Cross-talk between ILC2 and Gata3^high T_regs locally constrains adaptive type 2 immunity. Science Immunology, 9(97), Article eadl1903. https://doi.org/10.1126/sciimmunol.adl1903

@article{f4d531172f06445d81872afa60dd6008,

title = "Cross-talk between ILC2 and Gata3high Tregs locally constrains adaptive type 2 immunity",

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.",

author = "Julie Stockis and Thomas Yip and Julia Moreno-Vicente and Oliver Burton and Youhani Samarakoon and Schuijs, {Martijn j.} and Shwetha Raghunathan and Celine Garcia and Weike Luo and Whiteside, {Sarah k.} and Shaun Png and Charlotte Simpson and Stela Monk and Ashley Sawle and Kelvin Yin and Johanna Barbieri and Panagiotis Papadopoulos and Hannah Wong and Hans-Reimer Rodewald and Timothy Vyse and Mckenzie, {Andrew n. j.} and Cragg, {Mark s.} and Matthew Hoare and Withers, {David r.} and Fehling, {Hans j{\"o}rg} and Rahul Roychoudhuri and Adrian Liston and Halim, {Timotheus y. f.}",

note = "Publisher Copyright: {\textcopyright} 2024 th authors, some rights reserved; exclusive licensee american association for the advancement of Science. no claim to original u.S. government Works.",

year = "2024",

month = jul,

day = "19",

doi = "10.1126/sciimmunol.adl1903",

language = "English",

volume = "9",

journal = "Science Immunology",

issn = "2470-9468",

publisher = "American Association for the Advancement of Science",

number = "97",

}

Stockis, J, Yip, T, Moreno-Vicente, J, Burton, O, Samarakoon, Y, Schuijs, MJ, Raghunathan, S, Garcia, C, Luo, W, Whiteside, SK, Png, S, Simpson, C, Monk, S, Sawle, A, Yin, K, Barbieri, J, Papadopoulos, P, Wong, H, Rodewald, H-R, Vyse, T, Mckenzie, ANJ, Cragg, MS, Hoare, M, Withers, DR, Fehling, HJ, Roychoudhuri, R, Liston, A & Halim, TYF 2024, 'Cross-talk between ILC2 and Gata3^high T_regs locally constrains adaptive type 2 immunity', Science Immunology, vol. 9, no. 97, eadl1903. https://doi.org/10.1126/sciimmunol.adl1903

TY - JOUR

T1 - Cross-talk between ILC2 and Gata3high Tregs locally constrains adaptive type 2 immunity

AU - Stockis, Julie

AU - Yip, Thomas

AU - Moreno-Vicente, Julia

AU - Burton, Oliver

AU - Samarakoon, Youhani

AU - Schuijs, Martijn j.

AU - Raghunathan, Shwetha

AU - Garcia, Celine

AU - Luo, Weike

AU - Whiteside, Sarah k.

AU - Png, Shaun

AU - Simpson, Charlotte

AU - Monk, Stela

AU - Sawle, Ashley

AU - Yin, Kelvin

AU - Barbieri, Johanna

AU - Papadopoulos, Panagiotis

AU - Wong, Hannah

AU - Rodewald, Hans-Reimer

AU - Vyse, Timothy

AU - Mckenzie, Andrew n. j.

AU - Cragg, Mark s.

AU - Hoare, Matthew

AU - Withers, David r.

AU - Fehling, Hans jörg

AU - Roychoudhuri, Rahul

AU - Liston, Adrian

AU - Halim, Timotheus y. f.

PY - 2024/7/19

Y1 - 2024/7/19

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85199142253&partnerID=8YFLogxK

U2 - 10.1126/sciimmunol.adl1903

DO - 10.1126/sciimmunol.adl1903

M3 - Article

SN - 2470-9468

VL - 9

JO - Science Immunology

JF - Science Immunology

IS - 97

M1 - eadl1903

ER -

Cross-talk between ILC2 and Gata3^high T_regs locally constrains adaptive type 2 immunity

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