The diversity of myeloid immune cells shaping wound repair and fibrosis in the lung

Abstract

In healthy circumstances the immune system coordinates tissue repair responses in a tight balance that entails efficient inflammation for removal of potential threats, proper wound closure, and regeneration to regain tissue function. Pathological conditions, continuous exposure to noxious agents, and even ageing can dysregulate immune responses after injury. This dysregulation can lead to a chronic repair mechanism known as fibrosis. Alterations in wound healing can occur in many organs, but our focus lies with the lung as it requires highly regulated immune and repair responses with its continuous exposure to airborne threats. Dysregulated repair responses can lead to pulmonary fibrosis but the exact reason for its development is often not known. Here, we review the diversity of innate immune cells of myeloid origin that are involved in tissue repair and we illustrate how these cell types can contribute to the development of pulmonary fibrosis. Moreover, we briefly discuss the effect of age on innate immune responses and therefore on wound healing and we conclude with the implications of current knowledge on the avenues for future research.

Fibrocytes, Wound Healing, and Corneal Fibrosis

“…This process parallels the one found in the differentiation from classical monocytes (proinflammatory phenotype) into nonclassical monocytes (prohealing phenotype), where nonclassical monocytes re-express CD16 while decreasing CD14 expression. 30 Fibrocytes also express other monocyte markers such as CD11a, CD11b, CD32, and CD64, reinforcing their possible origin from monocytes. 25 It is well known that macrophages originate from monocytes, and Hashimoto et al 31 show that both macrophages and fibrocytes express Hck and Lyn-Src family kinases-the expression of which is often cell lineage specific.…”

Bioengineered Platforms for Chronic Wound Infection Studies: How Can We Make Them More Human-Relevant?

“…Following wounding, microbial colonization or infection rapidly induce the host innate immune response (Grice and Segre, 2012;Strbo et al, 2014), in which neutrophils are the first inflammatory cells at the wound site (Wilgus et al, 2013). Neutrophils phagocytose microbes in the wound bed while secreting a plethora of cytokines, proteolytic enzymes (such as matrix metalloproteinases, elastase, cathepsin G) and antimicrobial peptides (Dale et al, 2008;Wilgus et al, 2013;Florez-Sampedro et al, 2018). Other immune cells, such as monocytes (which differentiate to macrophages) also play a role in phagocytosis while producing a range of cytokines and growth factors, including TNFα and interleukins (Dale et al, 2008;Florez-Sampedro et al, 2018).…”

“…Neutrophils phagocytose microbes in the wound bed while secreting a plethora of cytokines, proteolytic enzymes (such as matrix metalloproteinases, elastase, cathepsin G) and antimicrobial peptides (Dale et al, 2008;Wilgus et al, 2013;Florez-Sampedro et al, 2018). Other immune cells, such as monocytes (which differentiate to macrophages) also play a role in phagocytosis while producing a range of cytokines and growth factors, including TNFα and interleukins (Dale et al, 2008;Florez-Sampedro et al, 2018). Further, resident cells, such as keratinocytes produce antimicrobial peptides, recruit immune cells, and induce the production of cytokines, further contributing to the inflammatory cascade (Richmond and Harris, 2014;Albanesi et al, 2018).…”

Creation of RANKL mutants with low affinity for decoy receptor OPG and their potential anti‐fibrosis activity

“…However, there is no effective therapy to reverse chronic fibrosis currently. Fibroblasts and myofibroblasts are the most important cells involved in the production of ECM [17]. Fibroblasts and myofibroblasts are the most important cells involved in the production of ECM [17].…”

“…Taking pulmonary fibrosis as an example, lung transplantation is the only effective way to treat lung fibrosis at present [13,15,16]. Fibroblasts and myofibroblasts are the most important cells involved in the production of ECM [17]. Macrophages, which are also abundantly present in fibrotic tissue, however, have been shown to possess both profibrotic and antifibrotic properties leading to different phenotypes [18,19].…”