Caspase-recruitment domain 9 (CARD9) is an adaptor protein expressed in many cells, especially immune cells. It is crucial for the function of the innate and adaptive immune systems. CARD9 is located downstream of pattern recognition receptors (PRRs) and transduces signals involved in innate immunity, mainly through interactions with signaling molecules like NF-κB and MAPK, regulating inflammatory responses and oxidative stress via cytokine and chemokine production [1,4].

In mouse models, Card9 knockout (KO) has shown significant impacts. In myocardial infarction, Card9 KO in macrophages led to improved left ventricular function and reduced infarct scar size, likely by suppressing lipocalin 2 (Lcn2) expression [2]. In colitis models, CARD9 deficiency in neutrophils increased susceptibility to DSS-induced colitis due to mitochondrial dysfunction and premature neutrophil apoptosis [5]. In SKG mice (a model for experimental ankylosing spondylitis), Card9 -/-SKG mice showed reduced Th17 cell induction, arthritis, and spondylitis, indicating a role of CARD9 in neutrophil-mediated Th17 expansion and disease [3].

In conclusion, CARD9 plays essential roles in regulating immune responses, inflammation, and cell survival. Gene knockout mouse models have been instrumental in revealing its role in various disease conditions such as cardiovascular diseases, colitis, and ankylosing spondylitis. These findings provide insights into potential therapeutic targets for these diseases.

References:

1. Liu, Xuanyou, Jiang, Bimei, Hao, Hong, Liu, Zhenguo. 2022. CARD9 Signaling, Inflammation, and Diseases. In Frontiers in immunology, 13, 880879. doi:10.3389/fimmu.2022.880879. https://pubmed.ncbi.nlm.nih.gov/35432375/

2. Liu, Yan, Shao, Yi-Hui, Zhang, Jun-Meng, Du, Jie, Li, Yu-Lin. 2023. Macrophage CARD9 mediates cardiac injury following myocardial infarction through regulation of lipocalin 2 expression. In Signal transduction and targeted therapy, 8, 394. doi:10.1038/s41392-023-01635-w. https://pubmed.ncbi.nlm.nih.gov/37828006/

3. Rosenzweig, Holly L, Vance, Emily E, Asare-Konadu, Kofi, Caplan, Liron, Napier, Ruth J. 2024. Card9/neutrophil signalling axis promotes IL-17A-mediated ankylosing spondylitis. In Annals of the rheumatic diseases, 83, 214-222. doi:10.1136/ard-2022-223146. https://pubmed.ncbi.nlm.nih.gov/37813481/

4. Zhang, Haina, Wang, Yeling, Men, Hongbo, Liu, Quan, Cai, Lu. 2022. CARD9 Regulation and its Role in Cardiovascular Diseases. In International journal of biological sciences, 18, 970-982. doi:10.7150/ijbs.65979. https://pubmed.ncbi.nlm.nih.gov/35173530/

5. Danne, Camille, Michaudel, Chloé, Skerniskyte, Jurate, Marteyn, Benoit, Sokol, Harry. 2022. CARD9 in neutrophils protects from colitis and controls mitochondrial metabolism and cell survival. In Gut, 72, 1081-1092. doi:10.1136/gutjnl-2022-326917. https://pubmed.ncbi.nlm.nih.gov/36167663/