Periodic Reporting for period 3 - BARRIER BREAK (Breaking the barrier: How inflammation spreads from skin to joint)
Reporting period: 2023-01-01 to 2024-06-30
In one third of patients with psoriatic skin inflammation, the inflammation spreads from the skin to the joints. The mechanisms why inflammation spreads in some patients and in some patients not, is still unexplored. This project aims to understand the pathomechanisms of spreading of inflammation from the skin to the joint. It investigates immune cell migration orginating from the skin and their potential to initiate inflammation in the joints. Precious insights into these mechanisms of spreading of inflammation might impact on new strategies of preventive medicine to prevent spreading of inflammation and to prevent disease progression from psoriasis to psoriatic arthritis.
Mid-term scientific report:
Cell types migrating from the skin into the circulation and entering the synovium of the joints have been identified by scRNAseq. Results have been confirmed on protein level by FACS. Pathogenic factors have been identified in a cell dependent manner. In parallel, human entheseal tissue have been prepared for analysis. Tissue CyTOF panels for spatiotemporal characterization of spreading immune cells have been established and are now ready to use.
Cell types migrating from the skin into the circulation and entering the synovium of the joints have been identified by scRNAseq. Results have been confirmed on protein level by FACS. Pathogenic factors have been identified in a cell dependent manner. In parallel, human entheseal tissue have been prepared for analysis. Tissue CyTOF panels for spatiotemporal characterization of spreading immune cells have been established and are now ready to use.
The project is in time with all aims which have been raised in the original proposal. NicheSeq has to be replaced by a new technique of slideSeq which has been developed in the lab for the project. This technique allows RNA profiling in spatiotemporal manner on single-cell level. In the next step molecular targets for therapeutic targeting have to be identified and tested in in vivo applications.