Fms-Like Tyrosine Kinase 3-Independent Dendritic Cells Are Major Mediators of Th2 Immune Responses in Allergen-Induced Asthmatic Mice

International Journal of Molecular Sciences

SungJae Shin¹  Yeeun Bak²  Hongmin Kim²  Dahee Shim²  Joo-Heon Yoon³  Chang-Hoon Kim³  SangChul Park⁴  DaYeon Choi⁵ 

[1] Brain Korea 21 Program for Leading Universities and Students (PLUS) Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea;Department of Microbiology, Yonsei University College of Medicine, Seoul 03722, Korea;Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 03722, Korea;Department of Otorhinolaryngology-Head and Neck Surgery, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul 07441, Korea;Industry-Academic Cooperation Foundation, Hallym University, Chuncheon 24252, Korea;

关键词: allergic asthma;    dendritic cells;    Fms-like tyrosine kinase 3;    murine model;    OX40 ligand;    Th2 immune responses;   

DOI  :  10.3390/ijms21249508

来源: DOAJ

【 摘 要 】

Dendritic cells (DCs) are the main mediators of Th2 immune responses in allergic asthma, and Fms-like tyrosine kinase 3 ligand (Flt3L) is an important growth factor for the development and homeostasis of DCs. This study identified the DC populations that primarily cause the initiation and development of allergic lung inflammation using Fms-like tyrosine kinase 3 (Flt3) knockout (KO) mice with allergen-induced allergic asthma. We observed type 2 allergic lung inflammation with goblet cell hyperplasia in Flt3 KO mice, despite a significant reduction in total DCs, particularly CD103⁺ DCs, which was barely detected. In addition, bone marrow-derived dendritic cells (BMDCs) from Flt3 KO mice directed Th2 immune responses in vitro, and the adoptive transfer of these BMDCs exacerbated allergic asthma with more marked Th2 responses than that of BMDCs from wild-type (WT) mice. Furthermore, we found that Flt3L regulated the in vitro expression of OX40 ligand (OX40L) in DCs, which is correlated with DC phenotype in in vivo models. In conclusion, we revealed that Flt3-independent CD11b⁺ DCs direct Th2 responses with the elevated OX40L and are the primary cause of allergic asthma. Our findings suggest that Flt3 is required to control type 2 allergic inflammation.

【 授权许可】

Unknown