Fig. 10

Age-dependent regulation of immune cell marker genes. For each immune cell, we retrieved marker genes from various databases (range 61–194 genes for the mouse and 133–1574 genes for human cells) and compiled information for individual marker genes in supplementary Table S12. The data represent enrichment scores based on signal intensities for individual genes of 89 individual mouse and 414 individual human genomic data sets. The enrichment score of marker genes infers a change in immune cell activity with age. To obtain independent validation, we analyzed single cell RNAseq data of pulmonary immune cells. A Panel A1: Depicted are violin plots of an age-related increase of enrichment scores for 9 different immune cells of the mouse. Panel A2: Depicted are violin plots of age-related variation of enrichment scores among 9 individual immune cells based on single cell RNAseq data. B Panel B1: Depicted are violin plots of an age-related variation of enrichment scores for 9 different immune cells of the human test set. Panel B2: Depicted are violin plots of an age-related variation of enrichment scores for 9 different immune cells of the human validation set. C Regulation of immune cell marker genes. Shown are commonly expressed gene markers between various immune cells in the lung of aged mice. The full genes names are given in supplementary Table S10. D The mouse CD3-T-cell receptor complex. Depicted are 20 upregulated genes coding for the CD3-TCR complex in the aging lung of mice. Activation of the CD3-TCR requires phosphorylation of the immunoreceptor tyrosine-based activation motif (ITAMs), and the lymphocyte-specific protein tyrosine kinase (Lck) catalyzes this reaction. Initially, the protein tyrosine phosphatase receptor type C (Cd45) activates Lck, and this phosphatase dephosphorylates the inhibitory C-terminal tail of Lck. Upon its activation, Lck phosphorylates the Zeta chain of T cell receptor associated protein (Zap70) and the Zap70 kinase phosphorylates linker for activation of T cells (Lat) and the lymphocyte cytosolic protein 2 (Slp76), which functions as a scaffold for signaling molecules. Moreover, Cd4 and Cd8 act as co-receptors to amplify TCR signaling. The co-stimulatory molecules Cd28, Cd80, Icos and Icos-L in addition to cytokines stimulate T cells activation and differentiation. E Independent validation of 61 immune response genes of the mouse genome by single cell RNAseq. Based on single cell RNAseq, we confirmed the regulation of immune response genes among individual immune and other resident cells of the lung. We compared the genomes of animals aged 12 weeks to 96 week old ones and assessed the expression of 61 immune response genes among dendritic, alveolar and interstitial macrophages, CD4⁺ and CD8⁺ T-cells, B-cells, NK, eosinophilic granulocytes, endothelial, AT1 and AT2 cells. Statistical significance testing: “Wilcoxon rank-sum” test. ns: not significant, *p < 0.05, **p < 0.01, ***p < 0.001. M.: Macrophage