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

研究成果: 雜誌貢獻文章

24 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)1186-1195e6
期刊Journal of Allergy and Clinical Immunology
135
發行號5
DOIs
出版狀態已發佈 - 五月 1 2015
對外發佈Yes

    指紋

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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