Spatial mapping of innate lymphoid cells in human lymphoid tissues and lymphoma at single-cell resolution

Nathalie Van Acker, François-Xavier Frenois, Pauline Gravelle, Marie Tosolini, Charlotte Syrykh, Camille Laurent and Pierre Brousset ()
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Nathalie Van Acker: IUCT-Oncopole
François-Xavier Frenois: IUCT-Oncopole
Pauline Gravelle: IUCT-Oncopole
Marie Tosolini: Team 9 NoLymIT and Labex TOUCAN
Charlotte Syrykh: IUCT-Oncopole
Camille Laurent: IUCT-Oncopole
Pierre Brousset: IUCT-Oncopole

Nature Communications, 2025, vol. 16, issue 1, 1-27

Abstract: Abstract Innate lymphoid cells (ILC) distribution and compartmentalization in human lymphoid tissues are incompletely described. Through combined multiplex immunofluorescence, multispectral imaging, and advanced computer vision methods, we provide a map of ILCs at the whole-slide single-cell resolution level, and study their proximity to T helper (Th) cells. The results show that ILC2 predominates in thymic medulla; by contrast, immature Th cells prevail in the cortex. Unexpectedly, we find that Th2-like and Th17-like phenotypes appear before complete T cell receptor gene rearrangements in these immature thymocytes. In the periphery, ILC2 are more abundant in lymph nodes and tonsils, penetrating lymphoid follicles. NK cells are uncommon in lymphoid tissues but abundant in the spleen, whereas ILC1 and ILC3 predominate in the ileum and appendix. Under pathogenic conditions, a deep perturbation of both ILC and Th populations is seen in follicular lymphoma compared with non-neoplastic conditions. Lastly, all ILCs are preferentially in close proximity to their Th counterparts. In summary, our histopathology tool help present a spatial mapping of human ILCs and Th cells, in normal and neoplastic lymphoid tissues.

Date: 2025
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DOI: 10.1038/s41467-025-59811-1

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