Cd14-KO Mouse

CD14, a human monocyte differentiation antigen, is a pattern recognition receptor (PRR) that enhances innate immune responses. As a TLR co-receptor, it detects pathogen-associated molecular patterns, although it lacks an intracellular tail [1]. It's also involved in multiple signaling pathways, such as activating NFAT in a TLR4-independent manner to regulate myeloid cell life cycle and transporting inflammatory lipids to induce phagocyte hyperactivation [1].

CD14 has been found to be associated with various diseases. In atherosclerosis, atheroma-relevant 7-oxysterols can differentially upregulate CD14 expression in monocytic cells, which may contribute to the development of atherosclerotic lesions [2]. In autoimmune diseases, tolerogenic CD14+ myeloid cells could potentially be used as cell-based immunotherapy to promote peripheral tolerance [3]. In juvenile myelomonocytic leukemia, CD14++/CD16-monocyte fraction profiling may help distinguish molecular subgroups within the disease [4]. In HIV-associated neurocognitive impairment, CD14+CD16+ monocyte transmigration across the blood-brain barrier is associated with the disease despite viral suppression, suggesting these monocytes as potential therapeutic targets [5].

In conclusion, CD14 is crucial for innate immune responses and is involved in multiple disease-related processes. Studies on CD14 using in vivo models could potentially lead to a better understanding of its role in diseases like atherosclerosis, autoimmune diseases, juvenile myelomonocytic leukemia, and HIV-associated neurocognitive impairment, providing insights for developing new therapeutic strategies.

References:

1. Wu, Zhenghao, Zhang, Zhenxiong, Lei, Zehua, Lei, Ping. 2019. CD14: Biology and role in the pathogenesis of disease. In Cytokine & growth factor reviews, 48, 24-31. doi:10.1016/j.cytogfr.2019.06.003. https://pubmed.ncbi.nlm.nih.gov/31296363/

2. Kim, Bo-Young, Son, Yonghae, Kim, Byoung Joon, Eo, Seong-Kug, Kim, Koanhoi. 2023. Atheroma-Relevant 7-Oxysterols Differentially Upregulate Cd14 Expression. In International journal of molecular sciences, 24, . doi:10.3390/ijms241310542. https://pubmed.ncbi.nlm.nih.gov/37445719/

3. van Wigcheren, Glenn F, Roelofs, Daphne, Figdor, Carl G, Flórez-Grau, Georgina. 2021. Three distinct tolerogenic CD14+ myeloid cell types to actively manage autoimmune disease: Opportunities and challenges. In Journal of autoimmunity, 120, 102645. doi:10.1016/j.jaut.2021.102645. https://pubmed.ncbi.nlm.nih.gov/33901801/

4. Gadgeel, Manisha, Bagla, Shruti, Buck, Steven, Shamoun, Mark, Ravindranath, Yaddanapudi. 2020. CD14/16 monocyte profiling in juvenile myelomonocytic leukemia. In Pediatric blood & cancer, 67, e28555. doi:10.1002/pbc.28555. https://pubmed.ncbi.nlm.nih.gov/32648963/

5. Veksler, Veronica, Leon-Rivera, Rosiris, Fleysher, Lazar, Morgello, Susan, Berman, Joan W. 2024. CD14+CD16+ monocyte transmigration across the blood-brain barrier is associated with HIV-NCI despite viral suppression. In JCI insight, 9, . doi:10.1172/jci.insight.179855. https://pubmed.ncbi.nlm.nih.gov/39253970/