Cross-talk between ILC2 and Gata3 T locally constrains adaptive type 2 immunity.
(2024) Science immunology — Vol. 9, n° 97, p. eadl1903 (2024)
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Yip, Thomas 
Moreno-Vicente, Julia Burton, Oliver Halim, Timotheus Y F
- Abstract
- Regulatory T cells (T) control adaptive immunity and restrain type 2 inflammation in allergic disease. Interleukin-33 promotes the expansion of tissue-resident T and group 2 innate lymphoid cells (ILC2s); however, how T locally coordinate their function within the inflammatory niche is not understood. Here, we show that ILC2s are critical orchestrators of T function. Using spatial, cellular, and molecular profiling of the type 2 inflamed niche, we found that ILC2s and T engage in a direct (OX40L-OX40) and chemotaxis-dependent (CCL1-CCR8) cellular dialogue that enforces the local accumulation of Gata3 T, which are transcriptionally and functionally adapted to the type 2 environment. Genetic interruption of ILC2-T communication resulted in uncontrolled type 2 lung inflammation after allergen exposure. Mechanistically, we found that Gata3 T can modulate the local bioavailability of the costimulatory molecule OX40L, which subsequently controlled effector memory T helper 2 cell numbers. Hence, ILC2-T interactions represent a critical feedback mechanism to control adaptive type 2 immunity.
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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., et al. (2024). Cross-talk between ILC2 and Gata3 T locally constrains adaptive type 2 immunity. Science immunology, 9(97), eadl1903. https://doi.org/10.1126/sciimmunol.adl1903 (Original work published 2024)