title: Dermal Fibroblasts Promote Alternative Macrophage Activation Improving Impaired Wound Healing.
abstract: Tight control of inflammation is required for tissue repair and wound healing and depends on alternative polarization of macrophages as checkpoint for inflammatory resolution. Its perturbations lead to impaired regeneration. Administration of cells/cell factors capable of reversing inflammation and rescuing alternative polarization could be promising for treating inflammatory diseases. We show that human dermal fibroblasts (dFb) are ideal candidates for such a task by demonstrating a new function of these cells, which is modulating macrophage polarization. Coculture of dFb with human monocytes in vitro or injection of dFb into mice with thioglycollate-induced peritonitis favors alternative macrophage activation and reduces inflammation by releasing tumor necrosis factor-inducible gene 6 protein and Cox-2 products. Silencing these factors in dFb abolishes the reported effects, demonstrating their importance for immunomodulation. Importantly, in a model of delayed wound healing due to prolonged inflammation (db/db mice), administration of dFb improves defective tissue repair with augmentation of alternative macrophage polarization and inflammation resolution. Human dFb are low immunogenic cells, easy to obtain, and can be expanded extensively in vitro conserving their immunomodulatory capacity; this, together with our findings, suggests that dFb might represent an alternative for cell-based therapies of conditions characterized by excessive inflammation and delayed tissue repair.
authors.affiliation: Department of Dermatology, Allergology and Venerology, Leipzig University Medical Center, Leipzig, Germany.
authors.forename: Rubén A
authors.initials: RA
authors.lastname: Ferrer
authors.affiliation: Department of Dermatology, Allergology and Venerology, Leipzig University Medical Center, Leipzig, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Saalbach
authors.affiliation: Department of Dermatology, Allergology and Venerology, Leipzig University Medical Center, Leipzig, Germany.
authors.forename: Mike
authors.initials: M
authors.lastname: Grünwedel
authors.affiliation: Department of Dermatology, Allergology and Venerology, Leipzig University Medical Center, Leipzig, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Lohmann
authors.affiliation: Department of Dermatology, Allergology and Venerology, Leipzig University Medical Center, Leipzig, Germany.
authors.forename: Inka
authors.initials: I
authors.lastname: Forstreuter
authors.affiliation: Department of Dermatology, Allergology and Venerology, Leipzig University Medical Center, Leipzig, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Saupe
authors.affiliation: Department of Dermatology, Allergology and Venerology, Leipzig University Medical Center, Leipzig, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Wandel
authors.affiliation: Department of Dermatology, Allergology and Venerology, Leipzig University Medical Center, Leipzig, Germany; Transregio Collaborative Research Centre TRR67, German Research Foundation (Deutsche Forschungsgemeinschaft), University Leipzig and Technical University Dresden, Leipzig, Germany.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Simon
authors.affiliation: Department of Dermatology, Allergology and Venerology, Leipzig University Medical Center, Leipzig, Germany; Transregio Collaborative Research Centre TRR67, German Research Foundation (Deutsche Forschungsgemeinschaft), University Leipzig and Technical University Dresden, Leipzig, Germany. Electronic address: sandra.franz@medizin.uni-leipzig.de.
authors.forename: Sandra
authors.initials: S
authors.lastname: Franz
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D002454:Cell Differentiation / Q000502:physiology*; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000637:transplantation*; D006801:Humans; D007150:Immunohistochemistry; D008262:Macrophage Activation / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology; D011897:Random Allocation; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000473:pathology / Q000628:therapy*