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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.
Authors:
J Stockis, T Yip, J Moreno-Vicente, O Burton, Y Samarakoon, MJ Schuijs, S Raghunathan, C Garcia, W Luo, SK Whiteside, S Png, C Simpson, S Monk, A Sawle, K Yin, J Barbieri, P Papadopoulos, H Wong, H-R Rodewald, T Vyse, ANJ McKenzie, MS Cragg, M Hoare, DR Withers, HJ Fehling, R Roychoudhuri, A Liston, TYF Halim
Journal:
Sci Immunol
Citation info:
9(97):eadl1903
Publication date:
19th Jul 2024
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DOI