Cd109-KO Mouse

Cd109, a glycosylphosphatidylinositol-anchored glycoprotein, is a member of the α2-macroglobulin/C3,C4,C5 family of thioester-containing proteins. It has been identified on blood cells like activated T cells, platelets, and a subset of CD34+ bone marrow cells with megakaryocyte progenitors. Cd109 is associated with the transforming growth factor (TGF)-β signaling pathway, where it negatively regulates TGF-β signaling in keratinocytes [1]. It also potentially relates to signal transducer and activator of transcription-3 signaling and is involved in processes like cell proliferation.

Cd109-deficient mice have provided insights into its role in disease. In asthma, CD109-deficient mice had reduced airway hyperreactivity and eosinophilic inflammation along with lower Th2 cytokine expression compared to wild-type mice. Lung cDC2s from these mice had a poor ability to induce cytokine production in ex vivo DC-T cell cocultures, suppressing Th2 differentiation [2]. In pulmonary fibrosis, CD109-transgenic mice overexpressing CD109 showed 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 ACTA2 expression in human fetal lung fibroblast cells in vitro and reduced pulmonary fibrosis in bleomycin-treated wild-type mice in vivo [3].

In conclusion, Cd109 is a multifunctional protein that plays a significant role in regulating inflammatory responses, such as in asthma and pulmonary fibrosis, mainly through its negative regulation of the TGF-β signaling pathway. The use of Cd109-deficient and transgenic mouse models has been crucial in revealing its role in these disease conditions, providing potential therapeutic targets for related diseases.

References:

1. Mii, Shinji, Enomoto, Atsushi, Shiraki, Yukihiro, Murakumo, Yoshiki, Takahashi, Masahide. 2019. CD109: a multifunctional GPI-anchored protein with key roles in tumor progression and physiological homeostasis. In Pathology international, 69, 249-259. doi:10.1111/pin.12798. https://pubmed.ncbi.nlm.nih.gov/31219232/

2. Aono, Yuya, Suzuki, Yuzo, Horiguchi, Ryo, Takahashi, Masahide, Suda, Takafumi. . CD109 on Dendritic Cells Regulates Airway Hyperreactivity and Eosinophilic Airway Inflammation. In American journal of respiratory cell and molecular biology, 68, 201-212. doi:10.1165/rcmb.2022-0109OC. https://pubmed.ncbi.nlm.nih.gov/36215676/

3. Naoi, Hyogo, Suzuki, Yuzo, Miyagi, Asuka, Takahashi, Masahide, Suda, Takafumi. . CD109 Attenuates Bleomycin-induced Pulmonary Fibrosis by Inhibiting TGF-β Signaling. In Journal of immunology (Baltimore, Md. : 1950), 212, 1221-1231. doi:10.4049/jimmunol.2300285. https://pubmed.ncbi.nlm.nih.gov/38334455/