title: Human renal fibroblasts generate dendritic cells with a unique regulatory profile.
abstract: Fibroblasts reside within the renal interstitium in close proximity to neighbouring dendritic cells (DCs). It is likely that these cells have a central role in the maintenance and function of resident and infiltrating renal DCs, though studies to confirm this have been lacking. We investigated whether renal fibroblasts influence human DC generation and function. We found that co-culture with renal fibroblasts led to the generation of monocyte-derived dendritic cells (Fibro-DCs), with significantly reduced CD80, CD83 and CD86 but elevated B7H1 and B7DC expression. In addition, these Fibro-DCs displayed a reduced capacity to produce interleukin (IL)-12p40 and IL-12p70 but maintained normal levels of IL-23 and IL-27. Furthermore, IL-10 production was elevated, which together resulted in a regulatory DC population with a reduced capacity to stimulate allogenic T-cell proliferation and interferon γ production, while preserving IL-17A. Supernatant transfer experiments suggested that a soluble mediator from the fibroblasts was sufficient to inhibit the immunogenic capability of DCs. Further experiments demonstrated that IL-6 was at least partially responsible for the modulating effect of renal fibroblasts on DC generation and subsequent function. In summary, renal fibroblasts may have a crucial decisive role in regulating local DC immune responses in vivo. Better understanding of this cell population and their mechanisms of action may have therapeutic relevance in many immune-driven renal diseases.
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Karen O
authors.initials: KO
authors.lastname: Dixon
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Laura
authors.initials: L
authors.lastname: Rossmann
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Sylvia W A
authors.initials: SW
authors.lastname: Kamerling
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Cees
authors.initials: C
authors.lastname: van Kooten
mesh_terms: D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers; D002450:Cell Communication; D002460:Cell Line; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D056747:Immunomodulation / Q000235:genetics; D007378:Interleukins / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060890:B7-H1 Antigen; D015415:Biomarkers; D007378:Interleukins