Increased phenotypic differentiation and reduced corticosteroid sensitivity of fibrocytes in severe asthma

Chun Yu Lo, Charalambos Michaeloudes, Pankaj K. Bhavsar, Chien Da Huang, Chun Hua Wang, Han Pin Kuo, Kian Fan Chung

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background Patients with severe asthma are less responsive to corticosteroid therapy and show increased airway remodeling. The mesenchymal progenitors, fibrocytes, may be involved in the remodeling of asthmatic airways. We propose that fibrocytes in severe asthma are different from those in nonsevere asthma. Objectives To examine the survival, myofibroblastic differentiation, and C-C chemokine receptor 7 (CCR7) expression in blood fibrocytes from patients with severe and nonsevere asthma and study the effect of corticosteroids on fibrocyte function. Methods The nonadherent non-T-cell fraction of blood mononuclear cells was isolated from healthy subjects and patients with nonsevere and severe asthma. Total and differentiating fibrocytes were identified by their expression of CD45, collagen I, and α-smooth muscle actin using flow cytometry. The expression of CCR7 and of the glucocorticoid receptor was measured by using flow cytometry. Results Increased numbers of circulating fibrocytes, with greater myofibroblastic differentiation potential, were observed in patients with severe asthma. Dexamethasone induced apoptosis, leading to reduction in the number of cultured fibrocytes and total nonadherent non-T cells from healthy subjects and patients with nonsevere asthma but not from patients with severe asthma. Dexamethasone reduced CCR7 expression in fibrocytes from patients with nonsevere asthma but not from patients with severe asthma. Glucocorticoid receptor expression was attenuated in fibrocytes from patients with severe asthma. Conclusions Patients with severe asthma have elevated numbers of circulating fibrocytes that show enhanced myofibroblastic differentiation and that are less responsive to the effects of corticosteroids.

Original languageEnglish
Pages (from-to)1186-1195e6
JournalJournal of Allergy and Clinical Immunology
Volume135
Issue number5
DOIs
Publication statusPublished - May 1 2015
Externally publishedYes

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Adrenal Cortex Hormones
Asthma
CC Chemokines
Chemokine Receptors
Airway Remodeling
Glucocorticoid Receptors
Dexamethasone
Healthy Volunteers
Flow Cytometry
Smooth Muscle
Actins
Blood Cells
Collagen
Apoptosis
Survival

Keywords

  • asthma
  • CCR7
  • corticosteroids
  • Fibrocytes
  • glucocorticoid receptor
  • myofibroblasts
  • nonadherent non-T cells
  • PBMCs
  • remodeling

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Increased phenotypic differentiation and reduced corticosteroid sensitivity of fibrocytes in severe asthma. / Lo, Chun Yu; Michaeloudes, Charalambos; Bhavsar, Pankaj K.; Huang, Chien Da; Wang, Chun Hua; Kuo, Han Pin; Chung, Kian Fan.

In: Journal of Allergy and Clinical Immunology, Vol. 135, No. 5, 01.05.2015, p. 1186-1195e6.

Research output: Contribution to journalArticle

Lo, Chun Yu ; Michaeloudes, Charalambos ; Bhavsar, Pankaj K. ; Huang, Chien Da ; Wang, Chun Hua ; Kuo, Han Pin ; Chung, Kian Fan. / Increased phenotypic differentiation and reduced corticosteroid sensitivity of fibrocytes in severe asthma. In: Journal of Allergy and Clinical Immunology. 2015 ; Vol. 135, No. 5. pp. 1186-1195e6.
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abstract = "Background Patients with severe asthma are less responsive to corticosteroid therapy and show increased airway remodeling. The mesenchymal progenitors, fibrocytes, may be involved in the remodeling of asthmatic airways. We propose that fibrocytes in severe asthma are different from those in nonsevere asthma. Objectives To examine the survival, myofibroblastic differentiation, and C-C chemokine receptor 7 (CCR7) expression in blood fibrocytes from patients with severe and nonsevere asthma and study the effect of corticosteroids on fibrocyte function. Methods The nonadherent non-T-cell fraction of blood mononuclear cells was isolated from healthy subjects and patients with nonsevere and severe asthma. Total and differentiating fibrocytes were identified by their expression of CD45, collagen I, and α-smooth muscle actin using flow cytometry. The expression of CCR7 and of the glucocorticoid receptor was measured by using flow cytometry. Results Increased numbers of circulating fibrocytes, with greater myofibroblastic differentiation potential, were observed in patients with severe asthma. Dexamethasone induced apoptosis, leading to reduction in the number of cultured fibrocytes and total nonadherent non-T cells from healthy subjects and patients with nonsevere asthma but not from patients with severe asthma. Dexamethasone reduced CCR7 expression in fibrocytes from patients with nonsevere asthma but not from patients with severe asthma. Glucocorticoid receptor expression was attenuated in fibrocytes from patients with severe asthma. Conclusions Patients with severe asthma have elevated numbers of circulating fibrocytes that show enhanced myofibroblastic differentiation and that are less responsive to the effects of corticosteroids.",
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N2 - Background Patients with severe asthma are less responsive to corticosteroid therapy and show increased airway remodeling. The mesenchymal progenitors, fibrocytes, may be involved in the remodeling of asthmatic airways. We propose that fibrocytes in severe asthma are different from those in nonsevere asthma. Objectives To examine the survival, myofibroblastic differentiation, and C-C chemokine receptor 7 (CCR7) expression in blood fibrocytes from patients with severe and nonsevere asthma and study the effect of corticosteroids on fibrocyte function. Methods The nonadherent non-T-cell fraction of blood mononuclear cells was isolated from healthy subjects and patients with nonsevere and severe asthma. Total and differentiating fibrocytes were identified by their expression of CD45, collagen I, and α-smooth muscle actin using flow cytometry. The expression of CCR7 and of the glucocorticoid receptor was measured by using flow cytometry. Results Increased numbers of circulating fibrocytes, with greater myofibroblastic differentiation potential, were observed in patients with severe asthma. Dexamethasone induced apoptosis, leading to reduction in the number of cultured fibrocytes and total nonadherent non-T cells from healthy subjects and patients with nonsevere asthma but not from patients with severe asthma. Dexamethasone reduced CCR7 expression in fibrocytes from patients with nonsevere asthma but not from patients with severe asthma. Glucocorticoid receptor expression was attenuated in fibrocytes from patients with severe asthma. Conclusions Patients with severe asthma have elevated numbers of circulating fibrocytes that show enhanced myofibroblastic differentiation and that are less responsive to the effects of corticosteroids.

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