An atlas of cells in the human tonsil

Massoni-Badosa, Ramon; Aguilar-Fernández, Sergio; Nieto, Juan C.; Soler-Vila, Paula; Elosua-Bayes, Marc; Marchese, Domenica; Kulis, Marta; Vilas-Zornoza, Amaia; Bühler, Marco Matteo; Rashmi, Sonal; Alsinet, Clara; Caratù, Ginevra; Moutinho, Catia; Ruiz, Sara; Lorden, Patricia; Lunazzi, Giulia; Colomer, Dolors; Frigola, Gerard; Blevins, Will; Romero-Rivero, Lucia; Jiménez-Martínez, Víctor; Vidal, Anna; Mateos-Jaimez, Judith; Maiques-Diaz, Alba; Ovejero, Sara; Moreaux, Jérôme; Palomino, Sara; Gomez-Cabrero, David; Agirre, Xabier; Weniger, Marc A.; King, Hamish W.; Garner, Lucy C.; Marini, Federico; Cervera-Paz, Francisco Javier; Baptista, Peter M.; Vilaseca, Isabel; Rosales, Cecilia; Ruiz-Gaspà, Silvia; Talks, Benjamin; Sidhpura, Keval; Pascual-Reguant, Anna; Hauser, Anja E.; Haniffa, Muzlifah; Prosper, Felipe; Küppers, Ralf; Gut, Ivo Glynne; Campo, Elias; Martin-Subero, José Ignacio; Heyn, Holger

doi:10.1016/j.immuni.2024.01.006

Cited by 13 publications

(3 citation statements)

References 144 publications

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“…In line with previous findings ( 48 – 52 ), we defined different architectural zones of the tonsil based on multiparametric staining (mantle zone: CD27 + , CD39 + ; GC: CD9 + , CD10 + , CD171+; non-GC: BCL-2 + , CD44 + ) ( Supplementary Figure S2C ). Expert marker-based gating using our analysis workflow allows definite cell annotation and quantification of immune cell subsets ( Figure 2E ), consistent with literature ( 53 ). Taken together, we validated an antibody panel of 121 markers using palatine tonsil tissue which serves as a platform to be adapted for a plethora of research questions.…”

Section: Resultssupporting

confidence: 87%

“…As a proof of concept, we describe the protein expression landscape of the tonsil in an unprecedented way, giving an extensive overview of immune cell subsets and their location. Other studies used tonsils as reference tissues before ( 26 , 72 ), but with smaller panels or at lower spatial resolution ( 53 ). We were able to detect and annotate not only common cell types by using the power of having many lineage-specific markers but also functional subpopulations like CD21 + germinal center B cells or CD11b + B cells.…”

Section: Discussionmentioning

confidence: 99%

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Unveiling spatial complexity in solid tumor immune microenvironments through multiplexed imaging

Scheuermann,

Kristmann,

Engelmann

et al. 2024

Front. Immunol.

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Deciphering cellular components and the spatial interaction network of the tumor immune microenvironment (TIME) of solid tumors is pivotal for understanding biologically relevant cross-talks and, ultimately, advancing therapies. Multiplexed tissue imaging provides a powerful tool to elucidate spatial complexity in a holistic manner. We established and cross-validated a comprehensive immunophenotyping panel comprising over 121 markers for multiplexed tissue imaging using MACSima™ imaging cyclic staining (MICS) alongside an end-to-end analysis workflow. Applying this panel and workflow to primary cancer tissues, we characterized tumor heterogeneity, investigated potential therapeutical targets, conducted in-depth profiling of cell types and states, sub-phenotyped T cells within the TIME, and scrutinized cellular neighborhoods of diverse T cell subsets. Our findings highlight the advantage of spatial profiling, revealing immunosuppressive molecular signatures of tumor-associated myeloid cells interacting with neighboring exhausted, PD1high T cells in the TIME of hepatocellular carcinoma (HCC). This study establishes a robust framework for spatial exploration of TIMEs in solid tumors and underscores the potency of multiplexed tissue imaging and ultra-deep cell phenotyping in unraveling clinically relevant tumor components.

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Section: Resultssupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Unveiling spatial complexity in solid tumor immune microenvironments through multiplexed imaging

Scheuermann,

Kristmann,

Engelmann

et al. 2024

Front. Immunol.

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show abstract

“…Paired scRNAseq and scCITEseq analysis was performed on Tfh cells (CD3 + CD4 + CD45RA - CD45RO + CXCR5 + ) from tonsils of adults with sleep apnea but otherwise ostensibly healthy (Figure S8A). Previous studies have identified 2-5 transcriptionally distinct Tfh populations, based on their migration and differentiation states, rather than by functional capacity 91,92 . Here, unsupervised Louvain clustering of 24393 Tfh cells identified 11 transcriptionally distinct Tfh clusters (C) (Figure 6A).…”

Section: Resultsmentioning

confidence: 99%

Divergent cytokine and transcriptional signatures control functional T follicular helper cell heterogeneity

Dalit,

Tan,

Sheikh

et al. 2024

Preprint

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SUMMARYAdaptive immune responses protect against multiple classes of pathogens, including viral, bacterial, fungal, and helminth infections. In all these settings, CD4+T follicular helper (Tfh) cells tailor high-affinity class-switched B cells responses. How Tfh lineage sovereignty is established while allowing for this context-specific functional heterogeneity is unclear. Here, we identify Tfh transcriptional networks in response to diverse infections. While Bcl-6 is the transcriptional linchpin of the core Tfh signature, this is overlayed with pathogen-specific transcriptional modules that shape Tfh function. Cytokine-transcriptional Tfh programing in mouse and human lymphoid tissue demonstrated that type I interferon and TGFβ signaling direct individual Tfh subpopulations to instruct B cell output. Here, we provide a transcriptional map and cell surface resource to interrogate Tfh diversity in humans and mice. This resource can be leveraged to further understand the origins of immune flexibility, perform immune monitoring in infection and antibody-mediated diseases and to develop context-specific vaccines.ONE-SENTENCE SUMMARYDalit, Tan and colleagues provide a resource that functionally and transcriptionally profiles T follicular helper cells (Tfh) during diverse pathogen responses to reveal a blueprint for transcriptional flexibility and new tools to interrogate Tfh heterogeneity in mice and humans.

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Human T follicular helper cells and their impact on IgE and IgG4 production across allergy, malignancy, and IgG4-related disease

Akiyama,

Alshehri,

Ishigaki

et al. 2024

Allergology International

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An atlas of cells in the human tonsil

Cited by 13 publications

References 144 publications

Unveiling spatial complexity in solid tumor immune microenvironments through multiplexed imaging

Unveiling spatial complexity in solid tumor immune microenvironments through multiplexed imaging

Divergent cytokine and transcriptional signatures control functional T follicular helper cell heterogeneity

Human T follicular helper cells and their impact on IgE and IgG4 production across allergy, malignancy, and IgG4-related disease

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