Role of dendritic cells in pulmonary fibrosis in mice

Tarrés, Meritxell Tort; Maus, Regina; Stolper, Jennifer; Aschenbrenner, Franziska; Welte, Tobias; Gauldie, Jack; Kolb, Martin; Maus, Ulrich A.

doi:10.1183/13993003.congress-2016.pa3891

Cited by 4 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistently, accumulated DCs in lung tissue were observed in mice with pulmonary fibrosis. Selective depletion of lung DCs markedly exacerbated lung fibrosis in mice, suggesting a protective role of lung DCs in fibrogenesis [ 59 ]. Furthermore, increased mobilization of lung CD11b + DC regulated pulmonary fibrosis development in mice [ 60 ].…”

Section: Innate Immune Cells In the Pathogenesis Of Fibrosismentioning

confidence: 99%

The Roles of Immune Cells in the Pathogenesis of Fibrosis

Huang

Peng

Xiao

et al. 2020

IJMS

View full text Add to dashboard Cite

Tissue injury and inflammatory response trigger the development of fibrosis in various diseases. It has been recognized that both innate and adaptive immune cells are important players with multifaceted functions in fibrogenesis. The activated immune cells produce various cytokines, modulate the differentiation and functions of myofibroblasts via diverse molecular mechanisms, and regulate fibrotic development. The immune cells exhibit differential functions during different stages of fibrotic diseases. In this review, we summarized recent advances in understanding the roles of immune cells in regulating fibrotic development and immune-based therapies in different disorders and discuss the underlying molecular mechanisms with a focus on mTOR and JAK-STAT signaling pathways.

show abstract

Section: Innate Immune Cells In the Pathogenesis Of Fibrosismentioning

confidence: 99%

The Roles of Immune Cells in the Pathogenesis of Fibrosis

Huang

Peng

Xiao

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Consistent with this, Dong et al showed that CD11c positive dendritic cells represent a major source of TNF early after renal IRI (24hours) 29 . The role of dendritic cells in kidney fibrosis has not been studied to our knowledge, however, dendritic cells and dendritic cell-derived TNF have been associated with fibrosis in the liver 30 ; in addition, dendritic cells are possibly also involved in lung fibrosis 31,32 .…”

Section: Discussionmentioning

confidence: 99%

“…However, the role of dendritic cells in kidney fibrosis has not been studied to our knowledge. Yet, dendritic cells and dendritic cell-derived TNF have been associated with fibrosis in the liver 34 and the lung 35,36 .…”

Section: Discussionmentioning

confidence: 99%

EGFR-driven profibrotic signals in AKI-to-CKD transition are blocked by TNF inhibition: Opportunities for etanercept treatment

Abdelmageed

Kefaloyianni

Arthanarisami

et al. 2021

Preprint

View full text Add to dashboard Cite

Inflammation is a key driver of fibrosis and progression of human chronic kidney disease (CKD), often caused or worsened by acute kidney injury (AKI-to-CKD transition). Sustained epidermal-growth-factor-receptor (EGFR) activation in injured proximal-tubule-cells (PTC) is strongly pro-inflammatory and has emerged as a key paradigm in AKI-to-CKD transition and CKD progression. Whether the key Type 1 inflammatory cytokine tumor-necrosis-factor (TNF) has a role in CKD progression and how TNF relates to the PTC-EGFR pathway is unknown, but retrospective analysis of patients using TNF biologic inhibitors suggests that TNF inhibition reduces incident CKD and CKD progression in humans. Here, we compared mice treated with control, TNF inhibition (murine etanercept, soluble TNF-scavenger), EGFR inhibition (erlotinib, EGFR-kinase-inhibitor) or their combination in an AKI-to-CKD bilateral renal-ischemia-reperfusion model. TNF- or EGFR-inhibition did not affect initial kidney injury, but significantly overlapped in reducing kidney injury-upregulated cytokines and equally strongly reduced kidney fibrosis, while combination treatment had no additive effect, suggesting EGFR and TNF act in the same fibrosis pathway. TNF exerted its profibrotic effects downstream of PTC-EGFR, as TNF-inhibition did not affect tubular EGFR activation in vivo. Consistent with this, TNF PTC-KO did not reduce inflammation or fibrosis, suggesting that PTC-derived TNF does not contribute to profibrotic PTC-EGFR activation. Kidney single-cell RNAseq analysis identified macrophages, dendritic cells and T cells, but not PTC, as dominant TNF sources after AKI. Only EGFR inhibition, but not TNF inhibition significantly blocked injury-induced kidney ingress of chemokine-receptor-2 (CCR2) positive cells and accumulation of macrophages, however, macrophage numbers where equal one month after AKI independent of treatment. Thus EGFR inhibition reduces ingress and accumulation of TNF-producing proinflammatory and profibrotic immune cells whereas TNF inhibition mechanistically largely acts by neutralizing their proinflammatory and profibrotic activities. Our work provides mechanistic background to motivate examination of TNF pathway inhibition in human AKI or CKD.

show abstract

“…The role of lung resident dendritic cells in pulmonary fibrosis remains largely unstudied. Single cell sequencing analysis of IPF lungs shows only minimal increases in dendritic cell population (132), while experimental modeling (adenoviral-TGFβ overexpression) indicates that fibrogenesis is accompanied by increases in CD11b + and CD103 + DCs, but that their ablation does not affect lung remodeling (277).…”

Section: Dendritic Cellsmentioning

confidence: 99%

Senescence in Pulmonary Fibrosis: Between Aging and Exposure

Venosa

2020

Front. Med.

View full text Add to dashboard Cite

Role of dendritic cells in pulmonary fibrosis in mice

Cited by 4 publications

References 0 publications

The Roles of Immune Cells in the Pathogenesis of Fibrosis

The Roles of Immune Cells in the Pathogenesis of Fibrosis

EGFR-driven profibrotic signals in AKI-to-CKD transition are blocked by TNF inhibition: Opportunities for etanercept treatment

Senescence in Pulmonary Fibrosis: Between Aging and Exposure

Contact Info

Product

Resources

About