Project Details
Projekt
Regulation of macrophage polarisation by fibroblasts - impact for the wound healing response
Subject Area
Dermatology
Term
from 2016 to 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 285654762
Dermal wound healing is a complex process occurring in three partially overlapping phases: inflammation, new tissue formation, tissue remodeling. An undisturbed healing response involves successive activation/differentiation and interaction of immune and tissue cells. Macrophages play an essential role in the wound healing process. Especially the controlled switch from inflammation-promoting M1 macrophages to immunoregulating M2 macrophages is of particular importance for inflammatory resolution and induction of new tissue formation. Wounds with a disturbed healing response are often associated with a defect transition from M1 to M2 macrophages. Mediators of the M1/M2 switch during the wound healing response are widely unknown. We have shown that signals from the dermal microenvironment modulate functions of immune cells. This includes fibroblasts producing a variety of cytokines and growth factors in crosstalk with immune cells of the wound. Fibroblast-derived factors contribute to the wound environment and regulate cell functions via paracrine and autocrine mechanisms. Several studies show a regulation of important fibroblast functions by macrophage derived mediators. In contrast, the impact of activated dermal fibroblasts on the function and polarization of macrophages has been not addressed to date. In preliminary data to this proposal we show that fibroblasts reduce the inflammatory response of M1 macrophages and promote differentiation of inflammatory triggered monocytes towards a M2 macrophage phenotype. We therefore hypothesize that fibroblasts play a critical role in inflammatory resolution during wound healing by regulating the switch from inflammatory M1 macrophages to immunoregulating M2 macrophages. This project will investigate whether and how dermal fibroblasts regulate the transition from M1 to M2 macrophages during the wound healing response and whether this regulation is affected in disturbed healing processes. Mechanisms how fibroblasts mediate their immunoregulatory effect on macrophages and during the wound healing response will be elucidated. Furthermore, it will be tested whether disturbed wound healing can be modulated by application of fibroblast.Aim of this project is to show whether and how fibroblasts of the microenvironment of the wound control the switch from M1 to M2 macrophages representing a crucial check point for inflammatory resolution during wound healing. These findings will substantially contribute to the understanding of the wound healing process. Based on this knowledge new therapeutic approaches for the modulation of disturbed healing responses will be developed.
DFG Programme
Research Grants
