The interaction of mesenchymal stromal cells and activated B cells in the context of fibrosis-associated autoimmune diseases, under special consideration of systemic sclerosis and CREST syndrome
Final Report Abstract
In the pathophysiology of SSc and similar autoimmune diseases accompanied by tissue remodeling, the interaction of activated immune cells with stromal cells, such as fibroblasts, plays an important but not yet sufficiently investigated role. The involvement of B cells in this process has so far been primarily viewed through their ability to produce autoantibodies that directly or indirectly promote fibrosis. However, there is evidence that B cells may also participate in the disease process through other properties, such as their ability to secrete cytokines. This project investigated whether and to what extent activated B cells might be involved in inflammation and fibrotic tissue remodeling. The results show that B cells stimulate skin fibroblasts to secrete pro-inflammatory cytokines and metalloproteases (MMPs). Blockade experiments with neutralizing antibodies showed that the B cell cytokines IL-1ß and TNFα are responsible for these effects. B cells also significantly inhibited the expression of alpha-SMA, an important marker for transdifferentiation into myofibroblasts, even in the presence of TGF- ß. They had no significant effect on collagen production. Addition of IL-4 to the cultures significantly reduced some of the B cell effects but did not lead to a pro-fibrotic effect. Differentiation of multipotent mesenchymal stromal cells in the presence of B cell factors favored osteogenesis. Adipogenesis was almost completely inhibited. The wnt signaling pathway, which was activated via B cells and is also thought to play a role in SSc, was identified to be upregulated during differentiation. These results provide new insights into the functions of B cells and the complex interplay between immune cells and mesenchymal cells in pathogenic tissue remodeling.
Publications
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P052 Effects of hypoxia and activated human B cells on immunosuppressive and differentiation capacity of multipotent mesenchymal stromal cells. Annals of the Rheumatic Diseases, 77, A34.
Scarpone, R.; Gitsioudis, P.; Saffrich, R.; Tykocinski, L.; Lorenz, H.-M. & Tretter, T.
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Activated human B cells modulate cytokine production and differentiation of multipotent mesenchymal stromal cells.European Workshop for Rheumatology Research 2019
Panagiotis Gitsioudis, B. Resch, P. Horn. R. Saffrich, R. Scarpone, L. Tycosinski. H.M. Lorenz & Th. Tretter
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Mesenchymal stromal cells retain their adipogenic differentiation potential after exposure to soluble factors of activated B-cells. European Workshop for Rheumatology Research 2020
Julia Schneider, Roberta Scarpone, Lars-Oliver Tykocinski, Hanns-Martin Lorenz & Theresa Tretter
