RRC ID 77569
Author Aono Y, Suzuki Y, Horiguchi R, Inoue Y, Karayama M, Hozumi H, Furuhashi K, Enomoto N, Fujisawa T, Nakamura Y, Inui N, Mii S, Takahashi M, Suda T.
Title CD109 on Dendritic Cells Regulates Airway Hyperreactivity and Eosinophilic Airway Inflammation.
Journal Am J Respir Cell Mol Biol
Abstract 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.
Volume 68(2)
Pages 201-212
Published 2023-2-1
DOI 10.1165/rcmb.2022-0109OC
PMID 36215676
MeSH Allergens Animals Asthma* / metabolism Cytokines / metabolism Dendritic Cells Disease Models, Animal Eosinophilia* / metabolism Inflammation / metabolism Mice Mice, Knockout Pyroglyphidae Th2 Cells
IF 5.373
Mice RBRC05911