PMID- 36215676
OWN - NLM
STAT- MEDLINE
DCOM- 20230202
LR  - 20230215
IS  - 1535-4989 (Electronic)
IS  - 1044-1549 (Linking)
VI  - 68
IP  - 2
DP  - 2023 Feb
TI  - CD109 on Dendritic Cells Regulates Airway Hyperreactivity and Eosinophilic Airway 
      Inflammation.
PG  - 201-212
LID - 10.1165/rcmb.2022-0109OC [doi]
AB  - Asthma is a chronic airway inflammatory disease characterized by airway 
      hyperreactivity (AHR) and eosinophilic airway inflammation. Dendritic cells (DCs) 
      are essential for the development of asthma via presenting allergens, causing 
      T-helper cell type 2 (Th2) skewing and eosinophil inflammation. Recent studies 
      have revealed that CD109, a glycosylphosphatidylinositol-anchored glycoprotein, 
      is involved in the pathogenesis of inflammatory diseases such as rheumatoid 
      arthritis and psoriasis. However, no study has addressed the role of CD109 in 
      asthma. This study sought to address the role of CD109 on DCs in the development 
      of AHR and allergic inflammation. CD109-deficient mice (CD109(-/-)) were 
      sensitized with house dust mite or ovalbumin and compared with wild-type mice for 
      induction of AHR and allergic inflammation. CD109-deficient mice had reduced AHR 
      and eosinophilic inflammation together with lower Th2 cytokine expression 
      compared with wild-type mice. Interestingly, CD109 expression was induced in lung 
      conventional DC2s (cDC2s), but not lung cDC1s, upon allergic challenge. Lung 
      cDC2s from CD109(-/-) mice had a poor ability to induce cytokine production in ex 
      vivo DC-T cell cocultures with high expression of RUNX3 (runt-related 
      transcription factor 3), resulting in suppression of Th2 differentiation. 
      Adoptive transfer of bone marrow-derived CD109(-/-) DCs loaded with house dust 
      mite failed to develop AHR and eosinophilic inflammation. Finally, administration 
      of monoclonal anti-CD109 antibody reduced airway eosinophils and significantly 
      decreased AHR. Our results suggest the involvement of CD109 in asthma 
      pathogenesis. CD109 is a novel therapeutic target for asthma.
FAU - Aono, Yuya
AU  - Aono Y
AD  - Second Division, Department of Internal Medicine, and.
FAU - Suzuki, Yuzo
AU  - Suzuki Y
AUID- ORCID: 0000-0001-6154-9791
AD  - Second Division, Department of Internal Medicine, and.
FAU - Horiguchi, Ryo
AU  - Horiguchi R
AD  - Advanced Research Facilities and Services, Hamamatsu University School of 
      Medicine, Hamamatsu, Japan.
FAU - Inoue, Yusuke
AU  - Inoue Y
AD  - Second Division, Department of Internal Medicine, and.
FAU - Karayama, Masato
AU  - Karayama M
AD  - Second Division, Department of Internal Medicine, and.
FAU - Hozumi, Hironao
AU  - Hozumi H
AUID- ORCID: 0000-0001-5439-1543
AD  - Second Division, Department of Internal Medicine, and.
FAU - Furuhashi, Kazuki
AU  - Furuhashi K
AD  - Second Division, Department of Internal Medicine, and.
FAU - Enomoto, Noriyuki
AU  - Enomoto N
AUID- ORCID: 0000-0003-3187-4264
AD  - Second Division, Department of Internal Medicine, and.
FAU - Fujisawa, Tomoyuki
AU  - Fujisawa T
AUID- ORCID: 0000-0002-8809-1781
AD  - Second Division, Department of Internal Medicine, and.
FAU - Nakamura, Yutaro
AU  - Nakamura Y
AD  - Second Division, Department of Internal Medicine, and.
FAU - Inui, Naoki
AU  - Inui N
AD  - Second Division, Department of Internal Medicine, and.
FAU - Mii, Shinji
AU  - Mii S
AD  - Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan; and.
FAU - Takahashi, Masahide
AU  - Takahashi M
AD  - Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan; and.
AD  - International Center for Cell and Gene Therapy, Fujita Health University, 
      Toyoake, Japan.
FAU - Suda, Takafumi
AU  - Suda T
AD  - Second Division, Department of Internal Medicine, and.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Allergens)
RN  - 0 (Cytokines)
RN  - Pulmonary Disease, Chronic Obstructive, Severe Early-Onset
SB  - IM
CIN - Am J Respir Cell Mol Biol. 2023 Feb;68(2):127-128. PMID: 36264767
MH  - Mice
MH  - Animals
MH  - Mice, Knockout
MH  - *Asthma/metabolism
MH  - Pyroglyphidae
MH  - *Eosinophilia/metabolism
MH  - Allergens
MH  - Cytokines/metabolism
MH  - Th2 Cells
MH  - Inflammation/metabolism
MH  - Dendritic Cells
MH  - Disease Models, Animal
OTO - NOTNLM
OT  - CD109
OT  - airway hyperreactivity
OT  - asthma
OT  - dendritic cell
OT  - eosinophil inflammation
EDAT- 2022/10/11 06:00
MHDA- 2023/02/03 06:00
CRDT- 2022/10/10 16:02
PHST- 2022/10/11 06:00 [pubmed]
PHST- 2023/02/03 06:00 [medline]
PHST- 2022/10/10 16:02 [entrez]
AID - 10.1165/rcmb.2022-0109OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2023 Feb;68(2):201-212. doi: 10.1165/rcmb.2022-0109OC.