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Spatial and functional specialization of human splenic innate lymphoid cells.

Created on 09 Sep 2026

Authors

Sarah J Colpitts, Sinthuja Jegatheeswaran, Siavash Mashhouri, Ash Hagerman, Mahmoud El-Maklizi, Humaira Murshed, Martin L Mak, Kyle T Reid, Julia M Murphy, Jessica A Mathews, Clinton S Robbins, Sarah Q Crome

Published in

Nature communications. Volume 17. Issue 1. Aug 11, 2026. Epub Aug 11, 2026.

Abstract

Secondary lymphoid organs, including the spleen, integrate innate and adaptive immune responses. Studies in murine models and humans highlight Natural Killer (NK) cells and other innate lymphoid cells (ILC) as key organizers of splenic immune activity, yet their in situ organization and interactions within immune networks are incompletely understood. Here, we report a spatially resolved single-cell atlas of human splenic NK cells and ILCs. We identify CD39+TIGIT+CD56bright NK cells that localize with alternatively activated macrophages outside of B cell follicles. Splenic ILC2s, enriched in vascular-associated regions, express CD40L and can promote B cell survival and IgA secretion. Finally, we define three spatially and functionally distinct ILC3 subsets, namely KLF2⁺ progenitor-like ILC3s, follicle-associated CD38⁺ ILC3s, and IFNGR1⁺ ILC3s, that can promote B cell proliferation, IL-10 production, and IgG class switching. This spatially resolved atlas provides a comprehensive reference of human splenic ILC organization, specialization, and interaction networks.

PMID:
42711319
Bibliographic data and abstract were imported from PubMed on 09 Sep 2026.

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