TY  - JOUR
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
TI  - Cross-talk between ILC2 and Gata3high Tregs locally constrains adaptive type 2 immunity.
JO  - Science immunology
VL  - 9
IS  - 97
SN  - 2470-9468
CY  - Washington, DC
PB  - AAAS
M1  - DKFZ-2024-01507
SP  - eadl1903
PY  - 2024
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.
KW  - Animals
KW  - T-Lymphocytes, Regulatory: immunology
KW  - GATA3 Transcription Factor: immunology
KW  - GATA3 Transcription Factor: metabolism
KW  - Mice
KW  - Adaptive Immunity: immunology
KW  - Mice, Inbred C57BL
KW  - Lymphocytes: immunology
KW  - Immunity, Innate: immunology
KW  - Mice, Knockout
KW  - Th2 Cells: immunology
KW  - Female
KW  - GATA3 Transcription Factor (NLM Chemicals)
KW  - Gata3 protein, mouse (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39028828
DO  - DOI:10.1126/sciimmunol.adl1903
UR  - https://inrepo02.dkfz.de/record/291771
ER  -