Abstract
This review provides a concise summary of the changing phenotypes of macrophages and fibroblastic cells during the local inflammatory response, the onset of tissue repair, and the resolution of inflammation which follow injury to an organ. Both cell populations respond directly to damage and present coordinated sequences of activation states which determine the reparative outcome, ranging from true regeneration of the organ to fibrosis and variable functional deficits. Recent work with mammalian models of organ regeneration, including regeneration of full‐thickness skin, hair follicles, ear punch tissues, and digit tips, is summarized and the roles of local immune cells in these systems are discussed. New investigations of the early phase of amphibian limb and tail regeneration, including the effects of pro‐inflammatory and anti‐inflammatory agents, are then briefly discussed, focusing on the transition from the normally covert inflammatory response to the initiation of the regeneration blastema by migrating fibroblasts and the expression of genes for limb patterning.
Highlights
ROLES OF MACROPHAGES AND FIBROBLASTS IN WOUND REPAIR AND REGENERATIONMitogenic and other growth-promoting factors released after tissue injury from activated platelets and sequestration sites in the extracellular matrix (ECM) collectively produce an initial proliferative response during the early phase of inflammation which sets the stage for how the tissues will be repaired (Werner & Grose, 2003)
This review provides a concise summary of the changing phenotypes of macrophages and fibroblastic cells during the local inflammatory response, the onset of tissue repair, and the resolution of inflammation which follow injury to an organ
In addition to chemokines derived from platelets, nonspecific factors with damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), released from dying cells and microbial invaders respectively, and reactive oxygen species generated by cell injury all serve to activate both immune and mesenchymal cells locally
Summary
Mitogenic and other growth-promoting factors released after tissue injury from activated platelets and sequestration sites in the ECM collectively produce an initial proliferative response during the early phase of inflammation which sets the stage for how the tissues will be repaired (Werner & Grose, 2003). It is clear that fibroblasts and other mesenchymal cells respond to DAMPs and PAMPs, as well as to pro-inflammatory factors from macrophages, triggering growth, migration, and new synthetic activities in these cells which reinforce the local immune response and other aspects of inflammation (Bernardo & Fibbe, 2013; Nowarski, Jackson, & Flavell, 2017). Prolongation of this macrophage−fibroblast activation state is characteristic of fibrosis and maladaptive repair processes (Wynn, 2008). Fibroblasts of the intestinal wall express antigen-presenting components and can directly modulate local T cell functions and activate local T cell expansion (Nowarski et al, 2017)
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