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

Authors
 Sang Chul Park  ;  Dahee Shim  ;  Hongmin Kim  ;  Yeeun Bak  ;  Da Yeon Choi  ;  Joo-Heon Yoon  ;  Chang-Hoon Kim  ;  Sung Jae Shin 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.21(24) : 9508, 2020-12 
Journal Title
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 
Issue Date
2020-12
Keywords
Fms-like tyrosine kinase 3 ; OX40 ligand ; Th2 immune responses ; allergic asthma ; dendritic cells ; murine model
Abstract
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.
Files in This Item:
T202005980.pdf Download
DOI
10.3390/ijms21249508
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chang Hoon(김창훈) ORCID logo https://orcid.org/0000-0003-1238-6396
Shin, Sung Jae(신성재) ORCID logo https://orcid.org/0000-0003-0854-4582
Yoon, Joo Heon(윤주헌)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/181505
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