Fig. 4: The immune-stromal cell crosstalk recruits immune cells via CXCL12/CXCR4 axis mediated by PLA2G2A in BP patients.

a Volcano plot of gene features of the CCL19⁺ FB cluster in BP patients compared to HC. b Volcano plot of gene features of the APCDD1⁺ FB cluster in BP patients compared to HC. P-values in a and b were obtained using the two-sided Likelihood-ratio test and Bonferroni corrected (Seurat 4). c The feature plot and the bar chart showing PLA2G2A mRNA expression within total skin cells between BP (n = 5) and HC (n = 8). d Protein level of PLA2G2A in serum from BP (n = 73) and HC (n = 31) examined by ELISA. e Transwell assays were used to measure cell migration of THP1 (n = 9) and Jurkat (n = 9) cells treated by PLA2G2A recombinant protein. P-values in c–e were calculated using two-sided Mann–Whitney U-test. *P < 0.05, **P < 0.01, ****P < 0.0001. In the box plot c–e: Minima: Lower limit of the whisker. Maxima: Upper limit of the whisker. Center: Median line inside the box. The upper and lower box bounds represent the 25% and 75% percentile of data. f Representative images of a BP patient and HC stained by multicolored IHC; green represents PLA2G2A⁺ fibroblasts, red represents macrophages, and yellow represents CD3 T cells. scale bar = 50 μm. Data are from three independent experiments. g Circle plots of the inferred CXCL12-CXCR4 pathway among major cell types in the BP and HC groups. h Hierarchical plot showing inferred intercellular communication network of CXCL12-CXCR4 signaling in BP skin. i The PLA2G2A/CXCL12 gene pair co-expression (upper panel), and the gene expression correlation analysis in expressing both genes (lower panel) in fibroblasts. The correlation was measured using the Pearson correlation coefficient. P-values were calculated using two-sided Pearson correlation test. j Flow plots of CD3⁺ T cells from PBMCs showing the expression of CXCR4 treated by PLA2G2A recombinant protein (upper panel), and the frequency of CXCR4 (lower panel) in BP (n = 21) and HC (n = 13) groups. P-values were calculated using paired two-sided Student’s t-test. **P < 0.01. Each sample is represented as one dot.