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Nalin, A.

Publications and source records attributed to Nalin, A..

2 recordsLinked to original sources
bioRxiv2026

CD200R1 Marks a Branchpoint During Human Natural Killer Cell Development in Tonsils

Human natural killer (NK) cells arise from common innate lymphoid cell (ILC) progenitor and precursor populations that are selectively enriched within secondary lymphoid tissues (SLTs) and that complete their terminal differentiation through stages of progressively lineage-restricted downstream developmental intermediates. We identify two subsets of tonsil CD94/NKG2A+NKp80- (stage 4A) NK-cell development intermediates that show differential expression of the inhibitory receptor, CD200R1. Ex vivo single-cell transcriptomic, DNA methylation, phenotypic, and functional analyses demonstrate that CD200R1 stage 4A cells represent an immature, oligopotent precursor population enriched for tissue-resident and cytokine-responsive programs. In contrast, CD200R1- stage 4A cells show more restricted NK-cell developmental potential concomitant with features of mature NK cells. These findings help to refine the human NK cell developmental pathway in tonsils and highlight CD200R1 as a useful marker delineating an uncommitted developmental state linking microenvironmental cues to NK-cell maturation and plasticity.

immunology↗
bioRxiv2026

Mapping human natural killer cell development in tonsil

Secondary lymphoid tissue, including tonsil, supports human NK cell development, but the spatial organization and tissue niches that drive this differentiation remain undefined. Here, we used single cell analysis of cyclic immunofluorescence to generate a comprehensive atlas of human NK cell development in tonsil. By integrating regional localization, chemokine signaling, cytokine availability, and cell phenotype, we show that NK cell differentiation follows a reproducible spatial trajectory defined by stage-specific cell-cell interactions. CD34+ NK cell progenitors are found in the interfollicular domain in proximity to high endothelial venules, consistent with this route of progenitor entry into tissue. Mature NK cells are primarily found in the T cell-rich parafollicular domain, where they interact with other NK cells and T cell subsets. Local inflammation increases NK cell frequency in tissue through both proliferation of NK progenitors and increased frequency of mature NK cells. Finally, we identify a subset of tonsil stromal cells that support differentiation of NK cells in vitro and proliferation of NK precursors in situ. Together, these findings demonstrate that spatial localization defines human NK cell development and provide an in situ definition of niches that support human NK cell differentiation in tonsil.

immunology↗