Inhibition of DYRK1B suppresses inflammation in allergic contact dermatitis model and Th1/Th17 immune response
Issued Date
2023-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-85156130241
Pubmed ID
37120440
Journal Title
Scientific Reports
Volume
13
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.13 No.1 (2023)
Suggested Citation
Wongchang T., Pluangnooch P., Hongeng S., Wongkajornsilp A., Thumkeo D., Soontrapa K. Inhibition of DYRK1B suppresses inflammation in allergic contact dermatitis model and Th1/Th17 immune response. Scientific Reports Vol.13 No.1 (2023). doi:10.1038/s41598-023-34211-x Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/81400
Title
Inhibition of DYRK1B suppresses inflammation in allergic contact dermatitis model and Th1/Th17 immune response
Other Contributor(s)
Abstract
Allergic contact dermatitis (ACD) is a type IV hypersensitivity mainly mediated by Th1/Th17 immune response. Topical corticosteroid is currently the first-line treatment for allergic contact dermatitis (ACD) and systemic administration of immunosuppressive drugs are used in patients with severe disseminated cases. However, increased risk of adverse effects has limited their use. Thus, the development of a novel immunosuppressant for ACD with low toxicity is a challenging issue. In this study, we began our study by using a murine contact hypersensitivity (CHS) model of ACD to examine the immunosuppressive effects of DYRK1B inhibition. We found that mice treated with a selective DYRK1B inhibitor show reduced ear inflammation. In addition, a significant reduction of Th1 and Th17 cells in the regional lymph node upon DYRK1B inhibition was observed by FACS analysis. Studies in vitro further revealed that DYRK1B inhibitor does not only suppressed Th1 and Th17 differentiation, but also promotes regulatory T cells (Treg) differentiation. Mechanistically, FOXO1 signaling was enhanced due to the suppression of FOXO1Ser329 phosphorylation in the presence of DYRK1B inhibitor. Therefore, these findings suggest that DYRK1B regulates CD4 T cell differentiation through FOXO1 phosphorylation and DYRK1B inhibitor has a potential as a novel agent for treatment of ACD.