Skin fi broblasts are potent suppressors of infl ammation in experimental arthritis

Objectives Mesenchymal stromal cells (MSC) are characterised by their capacity to suppress immune reactions. This function was reported to be shared in vitro by fibut their role has been poorly investigated in vivo. This study explored whether fi broblasts isolated from skin may suppress the host immune response in a model of autoimmune disorder. Methods and Results It was fi rst confi rmed that skin fi broblasts lack the capacity to differentiate into osteoblasts or chondrocytes but possess the capacity to inhibit in vitro the proliferation of T lymphocytes. Fibroblasts also secrete modulatory molecules, in particular prostaglandin E2 and nitric oxide, similar to MSC. To assess their role in vivo, the collagen-induced arthritis model was used, and showed that similar to MSC the intravenous injection of fieffi ciently suppress clinical signs of arthritis and delay disease onset. This effect was associated with reduced infl ammation as refl ected by biological parameters and increased levels of IL-5, IL-10 and IL-13 in the spleens of treated mice. To characterise the mechanism of immunosuppression further, phenotypic analyses were performed and could not detect any induction of CD4 CD25 Foxp3 + regulatory T (Treg) cells. A population of CD4 IL-10 + T cells was, however, detected that was slightly increased after fi broblast injection and signifi cantly upregulated after MSC administration. Conclusions This study gives the fi rst evidence for an immunosuppressive role of fiin vivo, and strongly suggests that fi broblasts induce a T-helper type 2 immune profi le, although the possibility that IL-10-secreting Treg cells may be generated cannot be excluded.