Deletion of TNFAIP6 gene in human keratinocytes demonstrates a role for TSG-6 to retain hyaluronan inside epidermis

Data collected about TSG-6-/- human reconstructed epidermis (RHE): TSG-6 is an anti-inflammatory protein which interacts with hyaluronan (HA) in extracellular matrix between keratinocytes but its function is not well understood. As TSG-6 is more expressed under pathological conditions, it was studied using RHE stimulated with Th2 cytokines or RHE infected by dermatophytes. In both two inflammatory models, TSG-6 and HA are significantly overexpressed. In order to understand the role of TSG-6, immortalized N/TERT keratinocytes were edited using CRISPR/Cas9 and two TSG-6-/- clonal populations were created and compared to TSG-6+/+ keratinocytes. TSG-6-/- keratinocytes showed a migration ability slowdown relative to TSG-6+/+ cells. Moreover, even if TSG-6-/- RHE exhibit normal differentiation, morphology and transcriptome, an increased HA leakage in the underlying culture medium is measured, especially in inflammatory conditions. This drastic HA leakage is rescued when TSG-6 expressing keratinocytes are reintroduced in RHE. Results suggest an implication of TSG-6 in HA remodelling and retaining in epidermal extracellular matrix.