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The primary function of sebaceous glands (SGs) is to produce the lipid rich sebum and thereby contribute to hair and skin lubrication. Recent findings however revealed that SGs may have immunoregulatory functions as well. We performed spatial transcriptomics (ST) on lesional and autologous non-lesional human skin samples of patients with psoriasis (PsO), atopic dermatitis (AD). Differentially expressed genes were identified followed by pathway enrichment analysis. Finally, a meta-analysis was done using RNAseq data from SZ95 human sebocytes treated with a combination of IL17 and TNFa to mimic the effect of a PsO-like microenvironment. Besides confirming that SGs contribute to skin homeostasis with a cell type specific lipid metabolism, we identified a large set of genes that were so far not known to be expressed in in-vivo SGs. In PsO samples, keratinization and immune function related genes were differentially expressed. In addition, we found that SGs of both diseases may contribute to extracellular matrix remodeling and detected a different set of genes that may be causative for the decreased size and number of SGs in the two diseases. Therefore, SGs are not bystanders in chronic inflammatory skin diseases like PsO and AD, but may actively may modulate inflammation and extracellular matrix remodelling in a disease specific manner.