Cd109, a glycosylphosphatidylinositol-anchored glycoprotein, is a member of the α2-macroglobulin/C3,C4,C5 family of thioester-containing proteins. It is known to associate with transforming growth factor (TGF)-β receptors and negatively regulate TGF-β signaling, which is crucial in various biological processes and diseases. CD109 also potentially relates to signal transducer and activator of transcription-3 signaling and may influence processes like cytokine secretion, immune cell recruitment, and macrophage polarization [1,2].

In Cd109-deficient mice, epidermal hyperplasia and osteopenia were observed, indicating its role in maintaining physiological homeostasis [1]. In asthma, Cd109-deficient mice had reduced airway hyperreactivity and eosinophilic inflammation, with lung conventional DC2s from these mice showing a poor ability to induce cytokine production and suppress Th2 differentiation. Administration of anti-Cd109 antibody also decreased airway eosinophils and AHR, suggesting Cd109's involvement in asthma pathogenesis [3]. In bleomycin-induced pulmonary fibrosis, Cd109-transgenic mice overexpressing Cd109 had attenuated pulmonary fibrosis, preserved lung function, and reduced lung fibroblasts and myofibroblasts, while Cd109 -/- mice had comparable fibrosis to wild-type mice. Recombinant Cd109 protein inhibited TGF-β signaling and decreased pulmonary fibrosis in vivo [4].

In conclusion, Cd109 is a multifunctional protein that plays a significant role in maintaining physiological homeostasis and is involved in various disease conditions such as asthma and pulmonary fibrosis. Gene knockout mouse models have been instrumental in revealing these functions, providing insights into potential therapeutic targets for these diseases.