Fig. 6: Cytokine-guided TFH phenotypes are evident in human lymphoid tissue. | Nature Immunology

Fig. 6: Cytokine-guided TFH phenotypes are evident in human lymphoid tissue.

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

Fig. 6

a–e, scRNA-seq of sorted CD3+CD4+CD45RA−CD45RO+CXCR5+CD27+ human tonsillar TFH cells from three healthy adult donors. UMAP dimensional reduction of data depicting 11 clusters on the basis of Louvain clustering via the Jaccard similarity index (k = 9) (a). Overlay of the mean ranked scores of each pathogen-specific signature onto UMAP clusters (b). Mean of the ‘TotalScore’ from the singscore: simpleScore function collated for each cluster. Pathogen-specific upregulated signature genes used. Rank scores of pathogen-specific signatures for each pseudosample on the basis of cluster and individual donors (c). Influenza A versus LCMV (left); LCMV versus T. muris (middle); influenza A versus H. polygyrus (right). Heatmap of the mean rank scores of pathogen-specific signatures for each cluster (row-based z score of the mean rank score) (d). GSEA-vissE analysis for the comparison of C7 versus C8 (e). Top gene sets of selected clusters as bar plots of DE gene counts with corresponding gene statistics (FDR as color shade) from the DE analysis. GSEA was performed via the Hallmarks c2 (‘CP:REACTOME’, ‘CP:PID’, ‘CP:BIOCARTA’,‘CP:KEGG’) and c5 (‘GO:BP’,‘GO:MF’) collections from the MSigDB using a two-tailed approach correcting for multiple testing with the FDR adjusted to P ≤ 0.05. f, Ranked score of pathogen-specific signatures in human dataset TFH cells from donors in SARS-CoV-2 vaccine (n = 5), influenza vaccine (n = 1), malaria infection (adult n = 3, child n = 3), peanut allergy (n = 3), asthma (n = 4) and autoimmune contexts (healthy donor n = 6, systemic lupus erythematosus n = 8). Ranked scores normalized to the first time point for signatures. Data are presented as mean ± s.e.m. g, Visium spatial tonsil data displaying a ranked score of pathogen-specific signatures onto GCs highlighted by the core TFH cell signature. h, Xenium spatial human lymph node data displaying a ranked score of pathogen-specific signatures in TFH cells and GCs highlighted by the core TFH cell signature.

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