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

Autor: Joo Heon Yoon, Hongmin Kim, Sung Jae Shin, Da Yeon Choi, Dahee Shim, Sang Chul Park, Chang Hoon Kim, Bak Yeeun
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Adoptive cell transfer
medicine.medical_treatment
medicine.disease_cause
OX40 ligand
murine model
lcsh:Chemistry
Mice
0302 clinical medicine
Allergen
lcsh:QH301-705.5
Spectroscopy
Mice
Knockout
CD11b Antigen
Th2 immune responses
biology
hemic and immune systems
General Medicine
Flow Cytometry
Adoptive Transfer
Computer Science Applications
Integrin alpha M
Female
medicine.symptom
allergic asthma
Inflammation
Enzyme-Linked Immunosorbent Assay
Catalysis
Article
Allergic inflammation
Inorganic Chemistry
03 medical and health sciences
Immune system
Th2 Cells
medicine
Animals
dendritic cells
Physical and Theoretical Chemistry
Molecular Biology
Fms-like tyrosine kinase 3
business.industry
Growth factor
Organic Chemistry
Asthma
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Fms-Like Tyrosine Kinase 3
Immunology
biology.protein
business
030215 immunology
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 24
International Journal of Molecular Sciences, Vol 21, Iss 9508, p 9508 (2020)
ISSN: 1422-0067
DOI: 10.3390/ijms21249508
Popis: 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.
Databáze: OpenAIRE
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