Blood fibrocytes are recruited during acute exacerbations of chronic obstructive pulmonary disease through a CXCR4-dependent pathway

Dupin, Isabelle; Allard, Benoît; Ozier, A.; Maurat, Élise; Ousova, Olga; Delbrel, Eva; Trian, Thomas; Bui, Hoang-Nam; Dromer, C.; Guisset, Olivier; Blanchard, Élodie; Hilbert, Gilles; Vargas, Frédéric; Thumerel, Matthieu; Marthan, Roger; Girodet, Pierre‐Olivier; Berger, Patrick

doi:10.1016/j.jaci.2015.08.043

Cited by 60 publications

(70 citation statements)

References 27 publications

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“…We found an increased frequency of circulating fibrocytes (identified as CD45+Col1+ cells) in patients with active, untreated CP compared with healthy controls, although we could not demonstrate correlations or associations with disease‐related parameters (e.g., acute‐phase reactants), clinical manifestations, or specific disease phenotypes such as IgG4‐related cases. The peripheral fibrocyte concentrations observed in our study subjects are in the range of those reported in other conditions, although the results are often difficult to compare due to heterogeneous staining or isolation techniques . Notably, we also detected significant amounts of fibrocytes in biopsy samples from CP patients, where such cells were identified not only on the basis of their dual positivity for CD45 and proCol1 but also as proCol1+ cells coexpressing CXCR4, the receptor of CXCL12/SDF‐1, a chemokine that regulates fibrocyte homing .…”

Section: Discussionsupporting

confidence: 55%

Fibrocytes in Chronic Periaortitis: A Novel Mechanism Linking Inflammation and Fibrosis

Nicastro

Vescovini

Maritati

et al. 2019

Arthritis & Rheumatology

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Objective Chronic periaortitis (CP) is a rare disease characterized by periaortic and periiliac fibroinflammatory tissue. The pathogenic mechanisms leading to tissue accumulation and activation of fibroblasts are unclear. This study was undertaken to explore the role of fibrocytes, circulating precursors of tissue fibroblasts, in patients with CP. Methods We studied 44 patients with newly diagnosed CP and 30 healthy controls. Circulating fibrocytes were identified as Col1+CD45+ cells using flow cytometry. Retroperitoneal tissue biopsy samples from 9 CP patients were stained with anti–type I procollagen, anti‐CXCR4, and anti‐CD45 antibodies and analyzed by confocal microscopy to detect tissue‐infiltrating fibrocytes. Circulating levels and tissue expression of CXCL12, a CXCR4 ligand that promotes fibrocyte homing, were investigated using enzyme‐linked immunosorbent assay and immunohistochemistry, respectively. We also characterized T helper polarization in biopsy samples from CP patients and measured serum levels of a panel of cytokines that are hallmarks of T helper responses and capable of influencing fibrocyte differentiation. Results The frequency of circulating Col1+CD45+ fibrocytes was higher in patients than in controls (P = 0.0371). CD45+proCol1+ and CXCR4+proCol1+ cells were detected in all examined biopsy samples from CP patients. Serum levels of CXCL12 were also higher in CP patients than controls (P = 0.0056), and tissue‐infiltrating inflammatory cells intensely expressed CXCL12. Increased serum levels of Th2 cytokines (e.g., interleukin‐13 [IL‐13] and IL‐10) were found in patients, and immunohistochemistry revealed a dominant infiltration of GATA‐3+ cells, also indicating Th2 polarization; Th2‐skewed responses are known to promote fibrocyte differentiation. Conclusion Our findings indicate that fibrocytes are enriched in the peripheral blood of CP patients and infiltrate target lesions. The accumulation of fibrocytes in the pathologic tissue might be driven by CXCL12, and Th2‐skewed immune responses are likely to facilitate their differentiation.

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Section: Discussionsupporting

confidence: 55%

Fibrocytes in Chronic Periaortitis: A Novel Mechanism Linking Inflammation and Fibrosis

Nicastro

Vescovini

Maritati

et al. 2019

Arthritis & Rheumatology

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“…[22,23] Here, we confirmed that a major proportion of human fibrocytes (nearly 80%) in the peripheral blood of NEC patients expressed CXCR4. At the same time, the CXCR4 receptors were present at a high level in the serum samples from NEC patients, which was similar to observations in patients with fibrotic lung disease.…”

Section: Discussionsupporting

confidence: 74%

Circulating fibrocytes are involved in inflammation and leukocyte trafficking in neonates with necrotizing enterocolitis

et al. 2017

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Fibrocytes, ahematopoietic stem cell source of fibroblasts/myofibroblasts, were previously implicated to infiltrate into the intestinal and enhance inflammation.The aims of the present study were to elucidate the role of fibrocytes in necrotizing enterocolitis (NEC) pathogenesis and to explore the mechanisms by which fibrocytes contributed to the inflammatory responses.We investigated circulating and intestinal local fibrocytes from 32 patients with NEC, 8 patients with noninflammatory conditions of the gastrointestinal tract and 12 normal subjects.Significantly higher numbers of circulating fibrocytes were found in the peripheral blood from NEC patients than the controls (P < .01). Numerous fibrocytes were found infiltrating the NEC intestinal mucous membranes. The percentage of fibrocytes to total leukocytes in the NEC inflammatory lesions was significantly increased compared with the percentage in the noninflammatory gastrointestinal tract. The fibrocyte attractant chemokine C-X-C motif chemokine ligand 12 (CXCL12) was significantly increased in the plasma and was detectable in 80% of the peritoneal lavage fluid from NEC patients but not the controls. Furthermore, chemokine expression was increased in fibrocytes infiltrating and trafficking to leukocyte sites. In culture, lipopolysaccharide (LPS) induced a significant increase in the expression of the Toll-like receptor (TLR4) signal, with the upregulation of p38 in both the isolated fibrocytes and macrophages. Similarly, interleukin (IL)-1β induced increased the upregulation of the IL-6, tumor necrosis factor (TNF)-α, and intercellular cell adhesion molecule-1 mRNAs but downregulated ColI in fibrocytes isolated from NEC patients compared with the controls.These findings indicate that circulating fibrocytes are increased in NEC patients and may be recruited to the inflammatory intestinal track, most likely through the CXCR4/CXCL12 axis. These cells may contribute to intestinal inflammation through TLR4 signaling by producing the TNF-α and IL-6 cytokines.

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“…To our knowledge, the later finding regarding COPD has not been previously described. Further studies are needed to confirm the underlying mechanisms of this association, but it can be hypothesized that pathological remodeling processes, as, for example, TGF-β signaling pathways or circulating fibroblasts, associated with ILD/IPF (34, 35) or COPD (36–39), may persist or be activated in some patients after LT and thus contribute to the higher risk of RAS.…”

Section: Discussionmentioning

confidence: 99%

Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation

Koutsokera¹,

Royer²,

Antonietti³

et al. 2017

Front. Med.

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BackgroundChronic lung allograft dysfunction and its main phenotypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), are major causes of mortality after lung transplantation (LT). RAS and early-onset BOS, developing within 3 years after LT, are associated with particularly inferior clinical outcomes. Prediction models for early-onset BOS and RAS have not been previously described.MethodsLT recipients of the French and Swiss transplant cohorts were eligible for inclusion in the SysCLAD cohort if they were alive with at least 2 years of follow-up but less than 3 years, or if they died or were retransplanted at any time less than 3 years. These patients were assessed for early-onset BOS, RAS, or stable allograft function by an adjudication committee. Baseline characteristics, data on surgery, immunosuppression, and year-1 follow-up were collected. Prediction models for BOS and RAS were developed using multivariate logistic regression and multivariate multinomial analysis.ResultsAmong patients fulfilling the eligibility criteria, we identified 149 stable, 51 BOS, and 30 RAS subjects. The best prediction model for early-onset BOS and RAS included the underlying diagnosis, induction treatment, immunosuppression, and year-1 class II donor-specific antibodies (DSAs). Within this model, class II DSAs were associated with BOS and RAS, whereas pre-LT diagnoses of interstitial lung disease and chronic obstructive pulmonary disease were associated with RAS.ConclusionAlthough these findings need further validation, results indicate that specific baseline and year-1 parameters may serve as predictors of BOS or RAS by 3 years post-LT. Their identification may allow intervention or guide risk stratification, aiming for an individualized patient management approach.

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Blood fibrocytes are recruited during acute exacerbations of chronic obstructive pulmonary disease through a CXCR4-dependent pathway

Abstract: Blood fibrocytes are recruited during COPD exacerbations and related to mortality and low lung function. The CXCL12/CXCR4 axis is involved in such fibrocyte recruitment (Firebrob study; ClinicalTrials NCT01196832).

Cited by 60 publications

References 27 publications

Fibrocytes in Chronic Periaortitis: A Novel Mechanism Linking Inflammation and Fibrosis

Fibrocytes in Chronic Periaortitis: A Novel Mechanism Linking Inflammation and Fibrosis

Circulating fibrocytes are involved in inflammation and leukocyte trafficking in neonates with necrotizing enterocolitis

Development of a Multivariate Prediction Model for Early-Onset Bronchiolitis Obliterans Syndrome and Restrictive Allograft Syndrome in Lung Transplantation

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