Dr. Chang, Ya-Jen 's orcid link picture Dr. Chang, Ya-Jen 's publons link picture


  • 02-27899050 (Lab) (Room No: N527)
  • 02-27898594 (Fax)

  1. Allergy and asthma
  2. Innate immunity and mucosal immunology
  3. 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

Staphylococcus aureus exacerbates dermal IL-33-ILC2 axis activation through evoking RIPK3/MLKL-mediated necroptosis of dry skin

Dr. Chang, Ya-Jen
JCI Insight, Feb 06, 2024

Atopic dermatitis (AD) is a persistent skin disease typified by symptoms of dry skin and recurrent eczema. AD patients are at heightened risk for Staphylococcus aureus (S. aureus) infection. Group 2 innate lymphoid cells (ILC2s) are mainly activated by epithelial cell-derived cytokines IL-33 and involved in the pathogenesis of AD. However, little is known about the effect of skin delipidization on the epithelial cell-derived cytokines and dermal ILC2s in AD. In our study, we investigated the mechanism by which S. aureus infection modulates and exacerbates the pathogenesis of dry skin, leading to type 2 inflammation in the context of innate immunity. In vivo, we found that S. aureus infection aggravated delipidization-induced dermal IL-33 release and dermal ILC2 accumulation, which exacerbated skin inflammation. We also noticed that Il33f/fK14cre mice and Tlr2-/- mice exhibited attenuated skin inflammation. In vitro, treatment with necroptosis inhibitors reduced IL-33 release from S. aureus-infected keratinocytes. Mechanistically, we observed an increase in the necroptosis-associated kinases, MLKL and RIPK3, in S. aureus-infected mice, indicating that IL-33 release was associated with necroptotic cell death responses. Our results reveal that S. aureus infection-elicited keratinocyte necroptosis contributes to IL-33-mediated type 2 inflammation, which exacerbates the pathogenesis of dry skin.