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Spatial and phenotypic geterogeneity of ILC subsets in mouse lung under type 2 inflammatory conditions

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Item Type:Article
Title:Spatial and phenotypic geterogeneity of ILC subsets in mouse lung under type 2 inflammatory conditions
Creators: Kroh, Sandy ORCID logoORCID: https://orcid.org/0000-0002-3736-3361, Pascual-Reguant, Anna ORCID logoORCID: https://orcid.org/0000-0002-5042-3699, Manukyan, Artür ORCID logoORCID: https://orcid.org/0000-0002-0441-9517, Uecker, Ralf, Günther, Robert, Philipsen, Lars ORCID logoORCID: https://orcid.org/0000-0001-5112-495X, Koehler, Ralf ORCID logoORCID: https://orcid.org/0000-0002-3660-1196, Mex, Peggy ORCID logoORCID: https://orcid.org/0009-0005-7567-1313, Landthaler, Markus ORCID logoORCID: https://orcid.org/0000-0002-1075-8734, Niesner, Raluca A. ORCID logoORCID: https://orcid.org/0000-0001-8969-5432 and Hauser, Anja E. ORCID logoORCID: https://orcid.org/0000-0002-7725-9526
Abstract:As key regulators of mucosal immunity, innate lymphoid cells (ILCs) are involved in tissue homeostasis, inflammation, and repair. Studying ILCs within their native microenvironment remains challenging due to the low abundance of these tissue-resident immune cells. Here, we applied cyclic multiplex immunofluorescence, namely multiepitope ligand cartography (MELC), in a systemic IL-33-induced type 2 inflammation model to spatio-temporally characterize ILC phenotype and localization in mouse lungs. Niche analysis with all identified cell types resulted in four distinct niches and an expansion of a mixed B and Plasma cell (BPC)/blood endothelial cell (BEC) niche, while the niche predominated by blood endothelial cells decreased at IL-33 day 3. Spatial neighborhood and coenrichment analyses revealed ILC2 accumulation in myeloid-rich peri-lymphatic niches at early time points of IL-33-mediated inflammation. ILC2s were in direct contact with activated alveolar macrophages and lymphatics. While they expressed ICOS under homeostatic conditions, pronounced expression of MHCII at days 1 and 3 of IL-33 stimulation was observed. Unlike ILC2s, NK cells/ILC1s were coenriched near blood vessels, next to B cells and plasma cells. Our findings demonstrate the utility of spatial multiplex imaging for dissecting rare immune cell localization and phenotypes and uncover dynamic, tissue-specific remodeling of ILC niches during early type 2 inflammation.
Keywords:IL-33, Innate Lymphoid Cells, Mucosal Immunology, Proteomics, Systemic Inflammation Model, Animals, Mice
Source:European Journal of Immunology
ISSN:0014-2980
Publisher:Wiley
Volume:56
Number:6
Page Range:e70223
Date:June 2026
Official Publication:https://doi.org/10.1002/eji.70223
PubMed:View item in PubMed
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