Involvement of fibrocytes in allergen-induced T cell responses and rhinovirus infections in asthma

Isgrò, Mirko; Bianchetti, Lorenza; Marini, Maurizio; Mattoli, Sabrina

doi:10.1016/j.bbrc.2013.06.099

Cited by 12 publications

(37 citation statements)

References 34 publications

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“…They circulate as a part of the peripheral blood mononuclear cell (PBMC) subpopulation of total leukocytes (Bucala et al, 1994;Chesney et al, 1998;Abe et al, 2001;Bianchetti et al, 2014) and have light scatter features on flow cytometry analysis similar to those of circulating myeloid dendritic cells (mDCs) and some myeloid progenitor cells (mPCs) (Bianchetti et al, 2014). They constitutively express some of the receptors that mediate the trafficking of other BMderived CD34 + PCs, mDCs, and eosinophils (Els) in asthma (Bellini et al, 2013;Mattoli, 2015), such as the C-X-C motif chemokine receptor 4 (CXCR4) (Abe et al, 2001), the C-C motif chemokine receptors (CCRs) CCR3, CCR5, and CCR7 (Abe et al, 2001;Isgrò et al, 2013a), and the receptor for interleukin (IL)-33 suppressor of tumorigenicity 2 (ST2) (Bianchetti et al, 2012a). Fcs have antigen-presenting function (Chesney et al, 1997;Isgrò et al, 2013b) and proinflammatory activities (Chesney et al, 1998;Bellini et al, 2012;Isgrò et al, 2013a;2013b) relevant to asthma (Mattoli, 2015).…”

Section: Background Information On Fc Identification and Isolationmentioning

confidence: 98%

“…They constitutively express some of the receptors that mediate the trafficking of other BMderived CD34 + PCs, mDCs, and eosinophils (Els) in asthma (Bellini et al, 2013;Mattoli, 2015), such as the C-X-C motif chemokine receptor 4 (CXCR4) (Abe et al, 2001), the C-C motif chemokine receptors (CCRs) CCR3, CCR5, and CCR7 (Abe et al, 2001;Isgrò et al, 2013a), and the receptor for interleukin (IL)-33 suppressor of tumorigenicity 2 (ST2) (Bianchetti et al, 2012a). Fcs have antigen-presenting function (Chesney et al, 1997;Isgrò et al, 2013b) and proinflammatory activities (Chesney et al, 1998;Bellini et al, 2012;Isgrò et al, 2013a;2013b) relevant to asthma (Mattoli, 2015). They participate in extracellular matrix (EM) remodeling through the production of some of the collagens and noncollagenous EM components synthesized in larger quantities by fibroblasts (Bucala et al, 1994;Chesney et al, 1998;Abe et al, 2001;Bianchetti et al, 2012b), and are also involved in collagen uptake and degradation (Bianchetti et al, 2012b).…”

Section: Background Information On Fc Identification and Isolationmentioning

confidence: 99%

“…+ monocytes that non-specifically bind antibodies against COL1 because they express receptors with a collagenous domain identical to that present in all secreted fibrillar collagens and intracellular collagen precursor protein (procollagens) (Isgrò et al, 2013a). This method also serves to distinguish Fcs from other cells at tissue sites because COL1-producing fibroblasts and macrophages containing phagocytized fragments of collagen in the cytoplasm are CD34-negative.…”

Section: Background Information On Fc Identification and Isolationmentioning

confidence: 99%

“…Its major limitation is that it precludes the isolation of a viable population of Fcs for functional analyses, because intracellular staining for COL1 requires prior cell fixation and permeabilization. To address this issue, novel multiple parameter approaches have been developed that allow for the identification and sorting of a pure population of circulating and tissue Fcs by flow cytometry on the basis of the coexpression at high levels on the cell surface of CD45/CD45RO, CD34, CD11b, and CD13 (Bianchetti et al, 2012a;Isgrò et al, 2013a;2013b), which is a distinctive feature of Fcs (Bucala et al, 1994;Chesney et al, 1998;Isgrò et al, 2013b;Bianchetti et al, 2014). Taking advantage of these technical improvements, it has been possible to uncover many functional properties of isolated Fcs and improve our understanding of the molecular mechanisms and signaling pathways involved in their trafficking and activation in asthma (Bellini et al, 2012;Bianchetti et al, 2012a;Isgrò et al, 2013a;2013b), as discussed below.…”

Section: Background Information On Fc Identification and Isolationmentioning

confidence: 99%

“…Thus, Fcs may contribute to the progression of fibrotic alterations every time there is a lack of asthma control and their effects persist as long as asthma control is not reachieved. Direct evidence of the contribution of Fcs to airway remodeling has been provided by tracking experiments in a mouse model of chronic allergic asthma with airway remodeling induced by repeated allergen exposures (Schmidt et al, 2003;Schmidt and Mattoli, 2013) and by assessing the effects of soluble factors present in the sputum of asthmatic patients on autologous circulating Fcs, including their migration, expression of the contractile protein α-SMA, and ability to release asthma-relevant EM molecules, in relation to the clinical characteristics and therapeutic responsiveness (Isgrò et al, 2013a). Moreover, in asthmatics with chronic bronchial obstruction, the numbers of circulating Fcs correlate with the previously recorded annual decline in lung function (Wang et al, 2008), suggesting that these cells may have contributed to generate irreversible alterations of the bronchial structure in such individuals.…”

Section: Contribution To Airway Remodeling In Persistent Asthmamentioning

confidence: 99%

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Pathogenetic and prognostic roles of bloodborne fibrocytes in asthma

Mattoli

2015

J. Zhejiang Univ. Sci. B

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Abstract:Bloodborne fibrocytes are cells mobilized from the bone marrow, which express surface antigens commonly ascribed to hematopoietic progenitors and have phenotypic and functional characteristics similar to those of immature mesenchymal cells. They exhibit predominant proinflammatory or profibrotic activities at tissue sites, depending on the host's response to environmental insults and on the characteristics of the cell infiltrate and cytokine milieu. In patients with allergic asthma, fibrocytes egress from the bone marrow and are recruited into the airways after every allergen exposure and during viral infections. Recruited fibrocytes amplify the inflammatory responses driven by T helper type 2 lymphokines and favor viral replication and further inflammation on respiratory virus infections. Persistently elevated blood fibrocyte counts and persisting airway fibrocytosis are present in patients with chronically undertreated or corticosteroid-insensitive asthma, and are linked to an enhanced risk of adverse outcomes because of the major involvement of fibrocytes in the development of structural abnormalities that lead to chronic airflow obstruction in these patients. Consequently, blood fibrocyte count is an emerging biomarker of asthma control and disease progression and its clinical applicability as a new outcome measure deserves further evaluation in large clinical trials.

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Section: Background Information On Fc Identification and Isolationmentioning

confidence: 98%

Section: Background Information On Fc Identification and Isolationmentioning

confidence: 99%

Section: Background Information On Fc Identification and Isolationmentioning

confidence: 99%

Section: Background Information On Fc Identification and Isolationmentioning

confidence: 99%

Section: Contribution To Airway Remodeling In Persistent Asthmamentioning

confidence: 99%

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Pathogenetic and prognostic roles of bloodborne fibrocytes in asthma

Mattoli

2015

J. Zhejiang Univ. Sci. B

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Migratory, metabolic and functional alterations of fibrocytes in type 2 diabetes

Walker¹,

Nissen²,

Geiger³

2018

IUBMB Life

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Fibrocytes are bloodborne mesenchymal progenitor cells that are recruited to injured tissue sites and contribute to the repair process by acquiring a myofibroblast-like phenotype and producing extracellular matrix components and growth factors. Treatment with normal fibrocytes or their exosomes restores the ability of genetically diabetic mice to heal skin wounds, suggesting the existence of dysfunctional alterations in diabetic fibrocytes. This study compared the migratory, metabolic and functional characteristics of fibrocytes from patients with type 2 diabetes (T2DPs) and healthy controls (HCs). It was found that the frequency of these cells was abnormally low in the peripheral blood of T2DPs. Diabetic fibrocytes showed reduced expression of the C-X-C motif and C-C motif chemokine receptors (CXCR)4, (CCR)5, and CCR7, and demonstrated reduced migration in response to their ligands (CXCL)12, (CCL)5, and CCL21. They exhibited increased expression of the receptor for advanced glycation end product, suppression of the alternative AGE receptor 1, increased intracellular concentrations of AGEs, decreased expression of sirtuin-1 and elevated oxidative stress. In short-term cultures, fibrocytes from T2DPs released larger amounts of proinflammatory cytokines than those from HCs. Unlike normal fibrocytes, diabetic fibrocytes did not exhibit increased expression of type I collagen and α-smooth muscle actin on stimulation with transforming growth factor (TGF)-β1 and this abnormal response was associated with downregulation of TGF-β1 type II receptor on the cell surface. Study findings uncover multiple migratory and functional alterations of diabetic fibrocytes that may contribute to explain why T2DPs experience impaired wound healing and chronic ulcers. © 2018 IUBMB Life, 70(11):1122-1132, 2018.

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Enumeration of circulating fibrocytes for clinical use in asthma by an optimized single-platform flow cytometry assay

Bianchetti¹,

Isgrò²,

Marini³

et al. 2014

BBA Clinical

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BackgroundElevated numbers of circulating fibrocytes are associated with inadequately controlled asthma, poor response to available therapies, and increased risk of adverse outcomes. The lack of reliable and clinically-applicable assays precludes a proper evaluation of blood fibrocyte count as a prognostic biomarker in asthma. This report concerns the use of a multiparameter flow cytometry assay for the enumeration of fibrocytes in the whole blood.MethodsConsenting fibrocyte donors were 19 patients with asthma well controlled by current treatment, 16 patients with treatment-resistant asthma, 9 patients with transiently uncontrolled asthma and 14 age-matched normal individuals. Blood sampling was performed once in patients with transiently uncontrolled asthma and twice, at an interval of one week, in the other subjects. The assay was performed in 100 μl of whole blood and involved a sequential gating strategy and absolute fibrocyte counting with a single instrument (single-platform assay).ResultsThe quantification of circulating fibrocytes by this assay was analytically and clinically valid. In individuals with stable clinical conditions, the repeatability of blood fibrocyte counts over one week was good. The intraclass correlation coefficient was 0.939 and 96.88% of the total variability reflected on-average differences among the tested subjects. Stabilized blood samples could be stored at 4 °C for up to 96 h before processing.ConclusionsThe novel assay for the enumeration of fibrocytes in the whole blood is reliable and clinically applicable.General significanceThis report demonstrates the validity and reliability of the first optimized assay for the enumeration of circulating fibrocytes in multicenter clinical trials.

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Involvement of fibrocytes in allergen-induced T cell responses and rhinovirus infections in asthma

Cited by 12 publications

References 34 publications

Pathogenetic and prognostic roles of bloodborne fibrocytes in asthma

Pathogenetic and prognostic roles of bloodborne fibrocytes in asthma

Migratory, metabolic and functional alterations of fibrocytes in type 2 diabetes

Enumeration of circulating fibrocytes for clinical use in asthma by an optimized single-platform flow cytometry assay

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