Cd93, also known as complement protein 1 q subcomponent receptor C1qR1 or C1qRp, is a transmembrane glycoprotein encoded by a gene on 20p11.21, composed of 652 amino acids. It exists in soluble (sCD93) and membrane-bound forms. Cd93 is mainly expressed on endothelial cells, where it promotes angiogenesis in both physiological and disease conditions like age-related macular degeneration and tumor angiogenesis. It is also expressed in hematopoietic stem cells, cytotrophoblast cells, platelets, and many immune cells, and is involved in modulating inflammatory-associated diseases and cardiovascular diseases [1].

In Cd93 -/- mice, primary melanoma growth was hampered, but metastatic dissemination was increased. This was associated with disrupted adherens and tight junctions in tumor endothelial cells and elevated matrix metalloprotease 9 expression at the metastatic site. Cd93 directly interacted with vascular endothelial growth factor receptor 2 (VEGFR2), and its absence led to VEGF-induced hyperphosphorylation of VEGFR2 in endothelial cells. Antagonistic anti-VEGFR2 antibody therapy rescued endothelial barrier function and reduced the metastatic burden in Cd93 -/- mice to wild-type levels, revealing a key role of Cd93 in maintaining vascular integrity in metastatic cancer [2]. In Il17d -/- mice, which are more susceptible to acute colitis, bacterial infection, and experimentally induced colon cancer, impaired IL-22 production by group 3 innate lymphoid cells (ILC3s) was observed. Protein purification studies showed that IL-17D bound to CD93 expressed on mature ILC3s, and mice lacking Cd93 in ILC3s also exhibited impaired IL-22 production and aggravated colonic inflammation, indicating an IL-17D-CD93 axis regulating ILC3 function to preserve intestinal homeostasis [3].

In conclusion, Cd93 plays essential roles in maintaining vascular integrity, regulating ILC3 function for intestinal homeostasis, and is involved in angiogenesis, inflammation, and tumor-related processes. The Cd93 -/- mouse models have been crucial in revealing its functions in metastatic cancer and colonic inflammation, providing insights into pathological angiogenesis and immune-related disease mechanisms.

References:

1. Tossetta, Giovanni, Piani, Federica, Borghi, Claudio, Marzioni, Daniela. 2023. Role of CD93 in Health and Disease. In Cells, 12, . doi:10.3390/cells12131778. https://pubmed.ncbi.nlm.nih.gov/37443812/

2. Vemuri, Kalyani, de Alves Pereira, Beatriz, Fuenzalida, Patricia, Lugano, Roberta, Dimberg, Anna. 2024. CD93 maintains endothelial barrier function and limits metastatic dissemination. In JCI insight, 9, . doi:10.1172/jci.insight.169830. https://pubmed.ncbi.nlm.nih.gov/38441970/

3. Huang, Jinling, Lee, Hae-Youn, Zhao, Xiaohong, Wang, Xiaohu, Dong, Chen. . Interleukin-17D regulates group 3 innate lymphoid cell function through its receptor CD93. In Immunity, 54, 673-686.e4. doi:10.1016/j.immuni.2021.03.018. https://pubmed.ncbi.nlm.nih.gov/33852831/