Dr. Chang, Ya-Jen
Research Fellow
- 02-27899050 (Lab) (Room No: N527)
- 02-27898594 (Fax)
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Specialty:
- Allergy and asthma
- Innate immunity and mucosal immunology
- Immunopharmacology
Education and Positions:
Ph.D., Pharmacology, National Taiwan University;
Instructor in Pediatrics, Harvard Medical School;
Research Associate in Immunology, Boston Children's Hospital
Highlight Detail
Pulmonary IL‐33 orchestrates innate immune cells to mediate RSV‐evoked airway hyperreactivity and eosinophilia
Dr. Chang, Ya-Jen
Allergy, Apr 21, 2020Background
Respiratory syncytial virus (RSV) infection is epidemiologically linked to asthma. During RSV infection, IL‐33 is elevated and promotes immune cell activation, leading to the development of asthma. However, which immune cells are responsible for triggering airway hyperreactivity (AHR), inflammation and eosinophilia remained to be clarified. We aimed to elucidate the individual roles of IL‐33‐activated innate immune cells, including ILC2s and ST2+ myeloid cells, in RSV infection‐triggered pathophysiology.
Methods
The role of IL‐33/ILC2 axis in RSV‐induced AHR inflammation and eosinophilia were evaluated in the IL‐33‐deficient and YetCre‐13 Rosa‐DTA mice. Myeloid‐specific, IL‐33‐deficient or ST2‐deficient mice were employed to examine the role IL‐33 and ST2 signaling in myeloid cells.
Results
We found that IL‐33‐activated ILC2s were crucial for the development of AHR and airway inflammation, during RSV infection. ILC2‐derived IL‐13 was sufficient for RSV‐driven AHR, since reconstitution of wild‐type ILC2 rescued RSV‐driven AHR in IL‐13‐deficient mice. Meanwhile, myeloid cell‐derived IL‐33 was required for airway inflammation, ST2+ myeloid cells contributed to exacerbation of airway inflammation, suggesting the importance of IL‐33 signaling in these cells. Local and peripheral eosinophilia is linked to both ILC2 and myeloid IL‐33 signaling.
Conclusions
This study highlights the importance of IL‐33‐activated ILC2s in mediating RSV‐triggered AHR and eosinophilia. In addition, IL‐33 signaling in myeloid cells is crucial for airway inflammation.