Cellular Plasticity of Inflammatory Myeloid Cells in the Peritoneal Foreign Body Response

Mooney, Jane; Rolfe, Barbara E.; Osborne, Geoffrey W.; Sester, David P.; Rooijen, Nico van; Campbell, Gordon; Hume, David; Campbell, Julie H.

doi:10.2353/ajpath.2010.090545

Cited by 85 publications

(81 citation statements)

References 43 publications

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“…Interestingly, a recent report suggested that tissue-infiltrating macrophages were capable of differentiating into myofibroblasts. 32 We did observe nominal overlap of GFP ϩ , Iba-1 ϩ macrophages with procollagen, suggesting that macrophages could acquire myofibroblast-like characteristics. Additional studies are needed to definitively address the frequency of myofibroblast transdifferentiation from macrophages/microglia in the context of CNS fibrosis.…”

Section: Discussionmentioning

confidence: 85%

Central Nervous System Fibrosis Is Associated with Fibrocyte-Like Infiltrates

Aldrich

Kielian

2011

The American Journal of Pathology

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Fibrotic wall formation is essential for limiting pathogen dissemination during brain abscess development. However, little is known about the regulation of fibrotic processes in the central nervous system (CNS). Most CNS injury responses are associated with hypertrophy of resident astrocytes, a process termed reactive gliosis. Studies of fibrosis outside the CNS have identified two bone marrow-derived cell types, fibrocytes and alternatively activated M2 macrophages, as key mediators of fibrosis. The current study used bone marrow chimeras generated from green fluorescent protein transgenic mice to evaluate the appearance of these cell types and whether bone marrowderived cells were capable of acquiring fibrotic characteristics during brain abscess development. Immunofluorescence staining revealed partial overlap between green fluorescent protein, ␣-smooth muscle actin, and procollagen, suggesting that a population of cells forming the brain abscess capsule originate from a bone marrow precursor. In addition, the influx of fibrocyte-like cells into brain abscesses immediately preceded the onset of fibrotic encapsulation. Fibrotic wall formation was also associated with increased numbers of alternatively activated M2 microglia and macrophages. To our knowledge, this is the first study demonstrating that bone marrow-derived infiltrates are capable of expressing fibrotic molecules during CNS inflammation.

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Section: Discussionmentioning

confidence: 85%

Central Nervous System Fibrosis Is Associated with Fibrocyte-Like Infiltrates

Aldrich

Kielian

2011

The American Journal of Pathology

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“…After obstructive injury, infiltrated T cells can produce chemokines and cytokines, which induce monocyte recruitment and amplify the inflammatory response (27,28). Profibrotic IL-4 is mainly produced by CD4 + Th2 cells, and antifibrotic IFN-g is primarily produced by CD4 + Th1 cells or CD8 + T cells in the regulation of fibrosis after injury (29,30).…”

mentioning

confidence: 99%

Depletion of CD8+ T Cells Exacerbates CD4+ T Cell–Induced Monocyte-to-Fibroblast Transition in Renal Fibrosis

Dong

Yang

Zhang

et al. 2016

The Journal of Immunology

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Bone marrow–derived monocyte-to-fibroblast transition is a key step in renal fibrosis pathogenesis, which is regulated by the inflammatory microenvironment. However, the mechanism by which the inflammatory microenvironment regulates this transition is not fully understood. In this study, we examined how the CD8+ T cell/IFN-γ microenvironment regulates the monocyte-to-fibroblast transition in renal fibrosis. Genetic ablation of CD8 promoted a monocyte-to-fibroblast transition and increased renal interstitial fibrosis, whereas reconstitution of CD8 knockout (KO) mice with CD8+ T cells decreased fibrosis. However, depletion of CD4+ T cells in CD8 KO mice also reduced fibrosis. To elucidate the role of CD4+ T cells in mediating CD8-regulated monocyte-to-fibroblast transition, CD4+ T cells were isolated from obstructed kidneys of CD8 KO or wild-type mice. CD4+ T cells isolated from CD8 KO obstructed kidney expressed more IL-4 and GATA3 and less IFN-γ and T-bet and showed increased monocyte-to-fibroblast transition in vitro compared with those isolated from wild-type obstructed kidney. To examine the role of IFN-γ–expressing CD8+ T cells, we reconstituted CD8 KO mice with CD8+ T cells isolated from IFN-γ KO mice. The IFN-γ KO CD8+ cells had no effect on IL-4, GATA3, IFN-γ, and T-bet mRNA expression in obstructed kidneys or renal fibrosis. Taken together, our findings identify the axis of CD8+ T cells and IFN-γ–CD4+ T cells as an important microenvironment for the monocyte-to-fibroblast transition, which negatively regulates renal fibrosis.

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“…The proportion of EGFP + α-SM actin + cells increased with time, reaching 51±1% of total cells (approx 80% of total α-SM actin + cells) at later stages of tissue development. The morphology of EGFP + -SM actin + cells also changed from a rounded macrophage-like appearance to a more spindle-shaped myofibroblastic phenotype, thus providing evidence that cells of myeloid origin can transdifferentiate to myofibroblasts (Mooney et al, 2010). These results are in agreement with those of Jabs et al (2005) who demonstrated that labelled peripheral blood mononuclear cells contributed to tissue capsule formation and that from day 14 onwards, a proportion of -SM actin-expressing spindleshaped cells co-expressed macrophage markers (ED1/ED2).…”

Section: What Is the Origin Of Foreign Body-induced Myofibroblasts?`mentioning

confidence: 87%

“…In contrast to the mouse where only a small proportion of cells express α-SM actin at day 14 (Mooney et al, 2010), at this time-point in rats, the majority of cells within the tissue capsule no longer express haemopoietic markers (CD45 or CD68) and most express myofibroblast markers α-SM actin and SM22 (Le et al, 2010). The essential role of macrophages in the peritoneal foreign body response was confirmed by experiments using MacGreen mice in which macrophage depletion with clodronate liposomes almost completely abrogated tissue capsule development (Mooney et al, 2010). We further showed that as the tissue capsule developed around foreign body implants in the peritoneal cavity, a sub-population of EGFP + cells appeared that co-expressed the myofibroblast marker α-SM actin.…”

Section: What Is the Origin Of Foreign Body-induced Myofibroblasts?`mentioning

confidence: 99%

“…Our laboratory also identified similar cells in the tissue capsule around foreign material (boiled blood clots) implanted in the peritoneal cavity (Campbell & Ryan, 1983;Mosse et al, 1985). To further investigate this hypothesis, we used transgenic 'MacGreen' mice (in which the enhanced green fluorescent protein (EGFP) transgene is driven by the colony stimulating factor-1 receptor (csf1r) proximal promotor to direct myeloid-restricted expression; Sasmono et al, 2003Sasmono et al, , 2007 to show that the majority of cells recruited to encapsulate the foreign body were of myeloid (monocyte/macrophage) origin (Mooney et al, 2010). Although a small subset of EGFP -cells, comprising mainly lymphocytes and mast cells was also observed, these cells are unlikely to contribute directly to fibrotic tissue formation.…”

Section: What Is the Origin Of Foreign Body-induced Myofibroblasts?`mentioning

confidence: 99%

See 1 more Smart Citation

The Fibrotic Response to Implanted Biomaterials: Implications for Tissue Engineering

Rolfe¹,

Mooney²,

Zhang³

et al. 2011

Regenerative Medicine and Tissue Engineering - Cells and Biomaterials

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Cellular Plasticity of Inflammatory Myeloid Cells in the Peritoneal Foreign Body Response

Cited by 85 publications

References 43 publications

Central Nervous System Fibrosis Is Associated with Fibrocyte-Like Infiltrates

Central Nervous System Fibrosis Is Associated with Fibrocyte-Like Infiltrates

Depletion of CD8+ T Cells Exacerbates CD4+ T Cell–Induced Monocyte-to-Fibroblast Transition in Renal Fibrosis

The Fibrotic Response to Implanted Biomaterials: Implications for Tissue Engineering

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