Journal Article

DKFZ-2024-01507

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cross-talk between ILC2 and Gata3high Tregs locally constrains adaptive type 2 immunity.

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.DKFZ* ; Vyse, T. ; McKenzie, A. N. J. ; Cragg, M. S. ; Hoare, M. ; Withers, D. R. ; Fehling, H. J. ; Roychoudhuri, R. ; Liston, A. ; Halim, T. Y. F.

2024
AAAS Washington, DC

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Please use a persistent id in citations: 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.

Keyword(s): Animals (MeSH) ; T-Lymphocytes, Regulatory: immunology (MeSH) ; GATA3 Transcription Factor: immunology (MeSH) ; GATA3 Transcription Factor: metabolism (MeSH) ; Mice (MeSH) ; Adaptive Immunity: immunology (MeSH) ; Mice, Inbred C57BL (MeSH) ; Lymphocytes: immunology (MeSH) ; Immunity, Innate: immunology (MeSH) ; Mice, Knockout (MeSH) ; Th2 Cells: immunology (MeSH) ; Female (MeSH) ; GATA3 Transcription Factor ; Gata3 protein, mouse

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Contributing Institute(s):

1. Zelluläre Immunologie (D110)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Essential Science Indicators ; IF >= 20 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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