CD109 on Dendritic Cells Regulates Airway Hyperreactivity and Eosinophilic Airway Inflammation.
Yuya AonoYuzo SuzukiRyo HoriguchiYusuke InoueMasato KarayamaHironao HozumiKazuki FuruhashiNoriyuki EnomotoTomoyuki FujisawaYutaro NakamuraNaoki InuiShinji MiiMasahide TakahashiTakafumi SudaPublished in: American journal of respiratory cell and molecular biology (2022)
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 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-/- mice) were sensitized with house dust mite (HDM) or ovalbumin and compared to wild-type (WT) mice for induction of AHR and allergic inflammation. CD109-deficient mice had reduced AHR and eosinophilic inflammation together with lower Th2 cytokine expression compared to WT 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, resulting in suppression of Th2 differentiation. Adoptive transfer of bone-marrow-derived CD109-/- DCs loaded with HDM 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.
Keyphrases
- dendritic cells
- oxidative stress
- rheumatoid arthritis
- chronic obstructive pulmonary disease
- allergic rhinitis
- stem cells
- immune response
- poor prognosis
- lung function
- adipose tissue
- metabolic syndrome
- type diabetes
- risk assessment
- bone marrow
- endothelial cells
- cystic fibrosis
- binding protein
- systemic sclerosis
- climate change
- drinking water
- cancer therapy
- case report