Deciphering the fate of slan<sup>+</sup>‐monocytes in human tonsils by gene expression profiling

Bianchetto-Aguilera, Francisco M.; Tamassia, Nicola; Gasperini, Sara; Calzetti, Federica; Finotti, Giulia; Gardiman, Elisa; Montioli, Riccardo; Bresciani, Debora; Vermi, William; Cassatella, Marco A.

doi:10.1096/fj.202000181r

Cited by 7 publications

(15 citation statements)

References 58 publications

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“…Tonsil 6-sulfo LacNAc + (slan + ) cells derive from non-classical monocytes and are distinct from cDC2 and macrophages. 91 Quantifying the slan + signature, 91 we identified four slan-like cell subpopulations, representing the most prevalent myeloid cell type in tonsils ( Figures 6 A–6C and S6 J). These slan-like cells included the following: (1) MMP cells expressing metalloproteinases and Toll-like receptors, (2) C1Q cells expressing complement members and class II MHC genes, (3) SELENOP cells expressing apolipoproteins and fucosidases, and (4) ITGAX cells expressing scavenger receptors ( Figure 6 D).…”

Section: Resultsmentioning

confidence: 99%

An atlas of cells in the human tonsil

Massoni-Badosa,

Aguilar-Fernández,

Nieto

et al. 2024

Immunity

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Section: Resultsmentioning

confidence: 99%

An atlas of cells in the human tonsil

Massoni-Badosa,

Aguilar-Fernández,

Nieto

et al. 2024

Immunity

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“…Tonsil 6-sulfo LacNAc+ (slan+) cells (hereafter named slancytes) have been described as a population derived from non-classical monocytes that is transcriptomically distinct from tonsillar cDC2 and macrophages (Bianchetto-Aguilera et al, 2020). In this setting, we investigated whether slancytes represent a single homogeneous population or, conversely, consist of several heterogeneous subsets.…”

Section: Non-lymphoid Cells and Novel Roles Of Slancyte Subsets In Hu...mentioning

confidence: 99%

“…In this setting, we investigated whether slancytes represent a single homogeneous population or, conversely, consist of several heterogeneous subsets. To that end, we quantified the slan+ cells, macrophage and cDC2 gene expression signatures (Bianchetto-Aguilera et al, 2020) for the 19 clusters of the myeloid compartment of our tonsil atlas. Strikingly, we identified four clusters that displayed a high expression of genes specifically upregulated in slan+ cells in comparison to tonsillar DCs and macrophages (Figure 6B and 6C).…”

Section: Non-lymphoid Cells and Novel Roles Of Slancyte Subsets In Hu...mentioning

confidence: 99%

An Atlas of Cells in the Human Tonsil

Massoni-Badosa

Soler-Vila

Aguilar-Fernández

et al. 2022

Preprint

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Palatine tonsils are secondary lymphoid organs representing the first line of immunological defense against inhaled or ingested pathogens. Here, we present a comprehensive census of cell types forming the human tonsil by applying single-cell transcriptome, epigenome, proteome and adaptive immune repertoire sequencing as well as spatial transcriptomics, resulting in an atlas of >357,000 cells. We provide a glossary of 121 annotated cell types and states, and disentangle gene regulatory mechanisms that drive cells through specialized lineage trajectories. Exemplarily, we stratify multiple tonsil-resident myeloid slancyte subtypes, establish a distant BCL6 superenhancer as locally active in both follicle-associated T and B cells, and describe SIX5 as a potentially novel transcriptional regulator of plasma cell maturation. Further, our atlas is a reference map to understand alterations observed in disease. Here, we discover immune-phenotype plasticity in tumoral cells and microenvironment shifts of mantle cell lymphomas (MCL). To facilitate such reference-based analysis, we develop HCATonsilData and SLOcatoR, a computational framework that provides programmatic and modular access to our dataset; and allows the straightforward annotation of future single-cell profiles from secondary lymphoid organs.

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“…The DEGs of clusters identified by k-means clustering analysis were examined using the “EnrichedDAVID” function of ClusterProfiler [ 27 ], considering exclusively the enrichment of KEGG pathways. Single-sample gene set enrichment analysis (ssGSEA) scores were calculated using the bioconductor/R package “GSVA” (function gsva -arguments: method = “ssgsea”, mx.diff = TRUE) as previously described [ 28 ]. The ssgsea enrichment scores were generated for each gene set of the significantly enriched KEGG pathways using the vst-transformed counts by DESeq2 (function vst -arguments: blind = FALSE).…”

Section: Methodsmentioning

confidence: 99%

SARS-CoV-2-Associated ssRNAs Activate Human Neutrophils in a TLR8-Dependent Fashion

Gardiman

Bianchetto-Aguilera

Gasperini

et al. 2022

Cells

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COVID-19 disease is characterized by a dysregulation of the innate arm of the immune system. However, the mechanisms whereby innate immune cells, including neutrophils, become activated in patients are not completely understood. Recently, we showed that GU-rich RNA sequences from the SARS-CoV-2 genome (i.e., SCV2-RNA1 and SCV2-RNA2) activate dendritic cells. To clarify whether human neutrophils may also represent targets of SCV2-RNAs, neutrophils were treated with either SCV2-RNAs or, as a control, R848 (a TLR7/8 ligand), and were then analyzed for several functional assays and also subjected to RNA-seq experiments. Results highlight a remarkable response of neutrophils to SCV2-RNAs in terms of TNFα, IL-1ra, CXCL8 production, apoptosis delay, modulation of CD11b and CD62L expression, and release of neutrophil extracellular traps. By RNA-seq experiments, we observed that SCV2-RNA2 promotes a transcriptional reprogramming of neutrophils, characterized by the induction of thousands of proinflammatory genes, similar to that promoted by R848. Furthermore, by using CU-CPT9a, a TLR8-specific inhibitor, we found that SCV2-RNA2 stimulates neutrophils exclusively via TLR8-dependent pathways. In sum, our study proves that single-strand RNAs from the SARS-CoV-2 genome potently activate human neutrophils via TLR8, thus uncovering a potential mechanism whereby neutrophils may contribute to the pathogenesis of severe COVID-19 disease.

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Deciphering the fate of slan⁺‐monocytes in human tonsils by gene expression profiling

Cited by 7 publications

References 58 publications

An atlas of cells in the human tonsil

An atlas of cells in the human tonsil

An Atlas of Cells in the Human Tonsil

SARS-CoV-2-Associated ssRNAs Activate Human Neutrophils in a TLR8-Dependent Fashion

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Deciphering the fate of slan+‐monocytes in human tonsils by gene expression profiling

Cited by 7 publications

References 58 publications

An atlas of cells in the human tonsil

An atlas of cells in the human tonsil

An Atlas of Cells in the Human Tonsil

SARS-CoV-2-Associated ssRNAs Activate Human Neutrophils in a TLR8-Dependent Fashion

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Deciphering the fate of slan⁺‐monocytes in human tonsils by gene expression profiling