Anti-IgE therapy inhibits chemotaxis, proliferation and transformation of circulating fibrocytes in patients with severe allergic asthma

Chun Hua Wang, Chih Ming Weng, Tzu Ting Huang, Meng Jung Lee, Chun Yu Lo, Mei Chuan Chen, Chung Liang Chou, Han Pin Kuo

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Background and objective: Circulating fibrocytes act as precursors of myofibroblasts, contribute to airway remodelling in chronic asthma and migrate to injured tissues by expressing CXCR4 and CCR7. Anti-IgE therapy improves severe allergic asthma (SAA) control and airway remodelling in T2-high SAA. The effects of anti-IgE therapy on fibrocyte activities were investigated in this study. Methods: The expression of CCR7, CXCR4, ST2 and α-SMA (α-smooth muscle actin) in both circulating and cultured fibrocytes from all patients with asthma was measured, and was repeated after omalizumab treatment in SAA. Fibrocytes recruitment, proliferation and transformation were also measured in response to anti-IgE therapy. Results: Omalizumab effectively improved asthma control and pulmonary function in T2-high SAA, associated with a decline in serum levels of IL-33 and IL-13. Omalizumab down-regulates CXCR4 and CCR7 expression of fibrocytes, which could suppress fibrocyte recruitment into the lungs. Omalizumab also suppressed the increased number of fibrocytes and α-SMA+ fibrocytes within the cultured non-adherent non-T (NANT) cells after 3–7 days of culture. The decrease in serum levels of IL-33 by omalizumab contributed to the effectiveness in inhibiting fibrocyte recruitment, proliferation and myofibroblast transformation through IL-33/ST2 axis. The elevated IL-13 expression in SAA patients potentiated the effects of IL-33 by increasing ST2 expression. Conclusion: Omalizumab reduced the number of circulating fibrocytes, cell and number of fibrocytes as well as α-SMA+ fibrocytes after 3–7 days of culture in SAA patients. IL-33 and IL-13 may be implicated in the effectiveness of omalizumab in inhibiting fibrocyte activation contributing partly to the clinical benefits in reducing lamina propria and basement membrane thickening.

Original languageEnglish
JournalRespirology
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • airway remodelling
  • anti-IgE therapy
  • chemokine receptors
  • chemotaxis
  • fibrocyte activation
  • omalizumab
  • severe allergic asthma

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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