Fibroblast heterogeneity: Keystone of tissue homeostasis and pathology in inflammation and ageing

Gauthier, Vincent; Kyriazi, Maria; Nefla, Meriam; Pucino, Valentina; Raza, Karim; Buckley, Christopher D.; Alsaleh, Ghada

doi:10.3389/fimmu.2023.1137659

Cited by 16 publications

(9 citation statements)

References 170 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Their cytokine production can influence the balance between pro-fibrotic and anti-fibrotic mechanisms in irradiated tissues ( 112 ). For example, a study has suggested that B cells can affect the fibrotic process by altering the cytokine milieu, impacting the activation and function of fibroblasts and immune cells ( 113 ). This role of B cells in fibrosis highlights the complexity of the immune response in radiation-induced skin damage and underscores the need for a comprehensive understanding of the adaptive immune responses in the development of effective treatments for fibrosis.…”

Section: Molecular Mechanisms Of Fibrosismentioning

confidence: 99%

Deciphering the fibrotic process: mechanism of chronic radiation skin injury fibrosis

Wang,

Chen,

Bao

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

This review explores the mechanisms of chronic radiation-induced skin injury fibrosis, focusing on the transition from acute radiation damage to a chronic fibrotic state. It reviewed the cellular and molecular responses of the skin to radiation, highlighting the role of myofibroblasts and the significant impact of Transforming Growth Factor-beta (TGF-β) in promoting fibroblast-to-myofibroblast transformation. The review delves into the epigenetic regulation of fibrotic gene expression, the contribution of extracellular matrix proteins to the fibrotic microenvironment, and the regulation of the immune system in the context of fibrosis. Additionally, it discusses the potential of biomaterials and artificial intelligence in medical research to advance the understanding and treatment of radiation-induced skin fibrosis, suggesting future directions involving bioinformatics and personalized therapeutic strategies to enhance patient quality of life.

show abstract

Section: Molecular Mechanisms Of Fibrosismentioning

confidence: 99%

Deciphering the fibrotic process: mechanism of chronic radiation skin injury fibrosis

Wang,

Chen,

Bao

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Notably, single‐cell RNA‐sequencing studies of oral mucosal tissues have demonstrated differences in the transcriptomic profile of fibroblast populations, a subset of which was enriched with chemotactic signatures including CXCL1 and CCL2 (Ko et al., 2023; Williams et al., 2021). While these studies highlight the underappreciated role of endogenous fibroblasts in immune modulation for maintaining homeostasis or in facilitating disease progression (S. Davidson et al., 2021; Gauthier et al., 2023), investigating specific inflammatory fibroblast subset has been difficult due to the lack of available in vivo mouse models.…”

Section: Introductionmentioning

confidence: 99%

Primed inflammatory response by fibroblast subset is necessary for proper oral and cutaneous wound healing

Chen,

Debnath,

Chikelu

et al. 2023

Molecular Oral Microbiology

View full text Add to dashboard Cite

Fibroblasts are ubiquitous mesenchymal cells that exhibit considerable molecular and functional heterogeneity. Besides maintaining stromal integrity, oral fibroblast subsets are thought to play an important role in host–microbe interaction during injury repair, which is not well explored in vivo. Here, we characterize a subset of fibroblast lineage labeled by paired‐related homeobox‐1 promoter activity (Prx1Cre+) in oral mucosa and skin and demonstrate these fibroblasts readily respond to microbial products to facilitate the normal wound healing process. Using a reporter mouse model, we determined that Prx1Cre+ fibroblasts had significantly higher expression of toll‐like receptors 2 and 4 compared to other fibroblast populations. In addition, Prx1 immunopositive cells exhibited heightened activation of inflammatory transcription factor NF‐κB during the early wound healing process. At the cytokine level, CXCL1 and CCL2 were significantly upregulated by Prx1Cre+ fibroblasts at baseline and upon LPS stimulation. Importantly, lineage‐specific knockout to prevent NF‐κB activation in Prx1Cre+ fibroblasts drastically impaired both oral and skin wound healing processes, which was linked to reduced macrophage infiltration, failure to resolve inflammation, and clearance of bacteria. Together, our data implicate a pro‐healing role of Prx1‐lineage fibroblasts by facilitating early macrophage recruitment and bacterial clearance.

show abstract

“…Under different pathological conditions, such as wound healing, malignancy, or other inflammatory disorders, normal fibroblasts can be activated and secrete cytokines to interact with other cells. Fibroblasts and other types of cells in the cutaneous EIME, such as epithelial cells, endothelial cells, pericytes, and adipocytes, can develop into myofibroblasts, or cancer-associated fibroblasts (CAFs) which are a heterogenous population of activated fibroblasts playing key roles in tumor microenvironment and affecting tumor proliferation, metastasis, and chemotherapy resistance ( Figure 1 ) ( 19 , 20 ). The activation states of fibroblasts are closely involved in the pathogenesis of diverse inflammatory skin diseases.…”

Section: Introductionmentioning

confidence: 99%

New insight into the role of fibroblasts in the epithelial immune microenvironment in the single-cell era

Wang,

Kou

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

The skin is exposed to environmental challenges and contains heterogeneous cell populations such as epithelial cells, stromal cells, and skin-resident immune cells. As the most abundant type of stromal cells, fibroblasts have been historically considered silent observers in the immune responses of the cutaneous epithelial immune microenvironment (EIME), with little research conducted on their heterogeneity and immune-related functions. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) have overcome the limitations of bulk RNA sequencing and help recognize the functional and spatial heterogeneity of fibroblasts, as well as their crosstalk with other types of cells in the cutaneous EIME. Recently, emerging single-cell sequencing data have demonstrated that fibroblasts notably participate in the immune responses of the EIME and impact the initiation and progression of inflammatory skin diseases. Here, we summarize the latest advances in the role of fibroblasts in the cutaneous EIME of inflammatory skin diseases and discuss the distinct functions and molecular mechanisms of activated fibroblasts in fibrotic skin diseases and non-fibrotic inflammatory skin diseases. This review help unveil the multiple roles of fibroblasts in the cutaneous EIME and offer new promising therapeutic strategies for the management of inflammatory skin diseases by targeting fibroblasts or the fibroblast-centered EIME.

show abstract

Fibroblast heterogeneity: Keystone of tissue homeostasis and pathology in inflammation and ageing

Cited by 16 publications

References 170 publications

Deciphering the fibrotic process: mechanism of chronic radiation skin injury fibrosis

Deciphering the fibrotic process: mechanism of chronic radiation skin injury fibrosis

Primed inflammatory response by fibroblast subset is necessary for proper oral and cutaneous wound healing

New insight into the role of fibroblasts in the epithelial immune microenvironment in the single-cell era

Contact Info

Product

Resources

About