Inhibition of DYRK1B suppresses inflammation in allergic contact dermatitis model and Th1/Th17 immune response

Thamrong Wongchang; Panwadee Pluangnooch; Suradej Hongeng; Adisak Wongkajornsilp; Dean Thumkeo; Kitipong Soontrapa

doi:10.1038/s41598-023-34211-x

Inhibition of DYRK1B suppresses inflammation in allergic contact dermatitis model and Th1/Th17 immune response

Sci Rep. 2023 Apr 29;13(1):7058. doi: 10.1038/s41598-023-34211-x.

Authors

Thamrong Wongchang^{1

2}, Panwadee Pluangnooch¹, Suradej Hongeng^{3

4}, Adisak Wongkajornsilp¹, Dean Thumkeo⁵, Kitipong Soontrapa⁶

Affiliations

¹ Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand.
² Division of Pharmacology, Department of Pharmaceutical Care, School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand.
³ Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
⁴ Excellent Center for Drug Discovery, Mahidol University, Bangkok, Thailand.
⁵ Department of Drug Discovery Medicine, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
⁶ Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand. kitipong.soo@mahidol.ac.th.

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 FOXO1^Ser329 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CD4-Positive T-Lymphocytes / pathology
Dermatitis, Allergic Contact*
Immunity
Immunosuppressive Agents / therapeutic use
Inflammation
Mice
Th17 Cells* / pathology

Substances

Immunosuppressive Agents