Anti-inflammatory pathways of catecholaminergic, tyrosine hydroxylase (TH) - positive cells in human and experimental arthritis

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In inflamed synovial tissue of patients and mice, tyrosine hydroxylase (TH) - positive cells (TH+ cells) were discovered in previous work in the applicant s group. These cells have a strong anti-inflammatory potential as described by the applicant s group in patients with rheumatoid arthritis (RA) and osteoarthritis. In recent work within Research Unit, mesenchymal stem cell (MSC) - derived TH+ cells had strong anti-inflammatory effects in the model of experimental collagen type II -induced arthritis. However, the exact sympathetic signalling pathway (whether adrenergic, dopaminergic, or purinergic [i.e., adenosine]) or the specific target cell of these sympathetic TH+ cells are not known.This project will delineate the sympathetic pathway responsible for anti-inflammatory effects of primary and MSC-derived TH+ cells using cell material of patients with RA / OA and arthritic mice. This project will also reveal the target cell responsible for anti-inflammatory effects in humans and mice. Knowledge of the sympathetic pathway will be used to treat animals with experimental arthritis in order to fully characterize the clinical ameliorating effect of TH+ cells. Finally, sympathetic differentiation techniques are applied to human lymphocytes of patients with RA to generate TH+ lymphocytes. These differentiated cells can be used as a platform for a cell-based therapy (use of MSC-derived TH+ cells or TH+ lymphocytes to treat RA).