PMID- 33327561
OWN - NLM
STAT- MEDLINE
DCOM- 20210315
LR  - 20210315
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 24
DP  - 2020 Dec 14
TI  - Fms-Like Tyrosine Kinase 3-Independent Dendritic Cells Are Major Mediators of Th2 
      Immune Responses in Allergen-Induced Asthmatic Mice.
LID - 10.3390/ijms21249508 [doi]
LID - 9508
AB  - 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.
FAU - Park, Sang Chul
AU  - Park SC
AUID- ORCID: 0000-0003-0384-8245
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Kangnam Sacred Heart 
      Hospital, Hallym University College of Medicine, Seoul 07441, Korea.
FAU - Shim, Dahee
AU  - Shim D
AD  - Department of Microbiology, Yonsei University College of Medicine, Seoul 03722, 
      Korea.
FAU - Kim, Hongmin
AU  - Kim H
AD  - Department of Microbiology, Yonsei University College of Medicine, Seoul 03722, 
      Korea.
AD  - Brain Korea 21 Program for Leading Universities and Students (PLUS) Project for 
      Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea.
FAU - Bak, Yeeun
AU  - Bak Y
AUID- ORCID: 0000-0003-3199-2754
AD  - Department of Microbiology, Yonsei University College of Medicine, Seoul 03722, 
      Korea.
AD  - Brain Korea 21 Program for Leading Universities and Students (PLUS) Project for 
      Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea.
FAU - Choi, Da Yeon
AU  - Choi DY
AD  - Industry-Academic Cooperation Foundation, Hallym University, Chuncheon 24252, 
      Korea.
FAU - Yoon, Joo-Heon
AU  - Yoon JH
AD  - Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 
      03722, Korea.
AD  - Global Research Laboratory for Allergic Airway Diseases, Yonsei University 
      College of Medicine, Seoul 03722, Korea.
AD  - The Airway Mucus Institute, Yonsei University College of Medicine, Seoul 03722, 
      Korea.
FAU - Kim, Chang-Hoon
AU  - Kim CH
AD  - Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 
      03722, Korea.
AD  - The Airway Mucus Institute, Yonsei University College of Medicine, Seoul 03722, 
      Korea.
FAU - Shin, Sung Jae
AU  - Shin SJ
AUID- ORCID: 0000-0003-0854-4582
AD  - Brain Korea 21 Program for Leading Universities and Students (PLUS) Project for 
      Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea.
AD  - Global Research Laboratory for Allergic Airway Diseases, Yonsei University 
      College of Medicine, Seoul 03722, Korea.
AD  - Department of Microbiology, Institute for Immunology and Immunological Diseases, 
      Yonsei University College of Medicine, Seoul 03722, Korea.
LA  - eng
GR  - 2016K1A1A2910779/Global Research Laboratory (GRL) Program/International
GR  - 2018R1C1B6007431/National Research Foundation funded by the Ministry of Science 
      and ICT, Korea/International
GR  - 2020R1I1A3067369/National Research Foundation funded by the Ministry of 
      Education, Korea/International
PT  - Journal Article
DEP - 20201214
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (CD11b Antigen)
RN  - 0 (OX40 Ligand)
RN  - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Asthma/*metabolism
MH  - CD11b Antigen/metabolism
MH  - Dendritic Cells/*metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Flow Cytometry
MH  - Mice
MH  - Mice, Knockout
MH  - OX40 Ligand/metabolism
MH  - Th2 Cells/*metabolism
MH  - fms-Like Tyrosine Kinase 3/genetics/*metabolism
PMC - PMC7765069
OTO - NOTNLM
OT  - Fms-like tyrosine kinase 3
OT  - OX40 ligand
OT  - Th2 immune responses
OT  - allergic asthma
OT  - dendritic cells
OT  - murine model
COIS- The authors declare no conflict of interest.
EDAT- 2020/12/18 06:00
MHDA- 2021/03/16 06:00
PMCR- 2020/12/14
CRDT- 2020/12/17 01:02
PHST- 2020/10/17 00:00 [received]
PHST- 2020/11/25 00:00 [revised]
PHST- 2020/12/10 00:00 [accepted]
PHST- 2020/12/17 01:02 [entrez]
PHST- 2020/12/18 06:00 [pubmed]
PHST- 2021/03/16 06:00 [medline]
PHST- 2020/12/14 00:00 [pmc-release]
AID - ijms21249508 [pii]
AID - ijms-21-09508 [pii]
AID - 10.3390/ijms21249508 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Dec 14;21(24):9508. doi: 10.3390/ijms21249508.