Fig. 8: The expansion of GZMK⁺CD8⁺ T cells in chronic inflammatory diseases and interaction with fibroblasts via CXCR4-CXCL12 axis.

a Schematic depicting the unbiased integration of 108,969 CD8⁺ T cells from 159 samples in 9 public ScRNA-seq datasets of healthy controls (HC) and diseased samples from atopic dermatitis (AD), eosinophilic esophagitis (EoE), allergic asthma, chronic obstructive pulmonary diseases (COPD), cystitis glandularis (CG), lupus erythematosus (LE), thyroiditis, sepsis, and hepatitis B virus (HBV) infection. Part of this figure was created by figdraw.com. CD8⁺ T subsets (b), the scaled expression of selected canonical markers (c) and expression of GZMK and GZMB (d) in the integrative dataset. e The percentage of GZMK⁺CD8⁺ T and GZMB⁺CD8⁺ T in the indicated group (sample size in each group is provided in (e) and in the Supplementary Table 18). Box plots show median, quantiles, minimum and maximum. Two-sided unpaired Wilcoxon test. AC allergic controls, Ag allergen challenge, Bln baseline, Dli administration of diluent, DLE discoid lupus erythematosus, HT Hashimoto’s thyroiditis, IRAE immune-related adverse events-thyroiditis, PN prurigo nodularis, SLE systemic lupus erythematosus, Sepsis_NS non-survivor of gram-negative sepsis, Sepsis_S survivor of gram-negative sepsis. f Total cells (left) and CD8⁺ T cells (right) from the GSE175930_EoE dataset. g Interactions of chemokine ligands (in structural cells) and receptors (in GZMK⁺CD8⁺ T) in the GSE175930_EoE dataset. P values are computed from one-sided permutation test (default for CellChat r-package). Dot size represents P value. The color represents communication possibility. h Total cells (left) and CD8⁺ T cells (right) from the GSE179633_LE_Dermis dataset. i Interactions of chemokine ligands (in structural cells) and receptors (in GZMK⁺CD8⁺ T) in the GSE179633_LE_Dermis dataset. P values are computed from one-sided permutation test (default for CellChat r-package). j Representative HE staining of the lesional skin (LS) section of AD from the GSE197023 dataset. AD_7, sample 7 of the AD group. k Co-expression pattern of GZMK⁺CD8⁺ T and fibroblasts in AD_7_LS section. l Total spots generated from all samples (n = 18 samples) of the GSE197023 dataset. m Neighborhood enrichment analysis between cell clusters in the LS group (n = 7 samples) of AD in the GSE197023 dataset. The “GZMK⁺CD8⁺ T cells” and “Fibroblasts/leukocyte infiltration (FB/Leu)” show a positive enrichment score. n Ligand-receptor interactions of CXCL12-CXCR4 from the structural cells to GZMK⁺CD8⁺ T cells in the LS group (n = 7 samples) of AD in the GSE197023 dataset. P values result from a one-sided permutation-based test with 1000 permutations and were adjusted with the Benjamini-Hochberg method. ECM extracellular matrix, MAIT mucosal associated invariant T cell, SMCs smooth muscle cells. Source data are provided as a Source Data file.