title: Skin fibroblasts are potent suppressors of inflammation in experimental arthritis.
abstract: OBJECTIVE
  Mesenchymal stromal cells (MSC) are characterised by their capacity to suppress immune reactions. This function was reported to be shared in vitro by fibroblasts but their role has been poorly investigated in vivo. This study explored whether fibroblasts isolated from skin may suppress the host immune response in a model of autoimmune disorder.
  
  
  RESULTS
  It was first confirmed that skin fibroblasts 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 fibroblasts efficiently suppress clinical signs of arthritis and delay disease onset. This effect was associated with reduced inflammation as reflected 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 fibroblast injection and significantly upregulated after MSC administration.
  
  
  CONCLUSIONS
  This study gives the first evidence for an immunosuppressive role of fibroblasts in vivo, and strongly suggests that fibroblasts induce a T-helper type 2 immune profile, although the possibility that IL-10-secreting Treg cells may be generated cannot be excluded.
authors.affiliation: Inserm U844, Hôpital Saint-Eloi, Montpellier, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Bouffi
authors.forename: Claire
authors.initials: C
authors.lastname: Bony
authors.forename: Christian
authors.initials: C
authors.lastname: Jorgensen
authors.forename: Danièle
authors.initials: D
authors.lastname: Noël
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000517:prevention & control*; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000276:immunology / Q000637:transplantation*; D007108:Immune Tolerance; D016130:Immunophenotyping; D007165:Immunosuppression Therapy / Q000379:methods*; D016753:Interleukin-10 / Q000096:biosynthesis; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D012867:Skin / Q000276:immunology*; D013154:Spleen / Q000276:immunology
chemical_list: D016753:Interleukin-10