Aim2, also known as Absent in melanoma 2, is a cytoplasmic sensor that recognizes double-strand DNA. It forms the AIM2 inflammasome, an important protein platform in cells. The AIM2 inflammasome initiates innate immune responses by cleaving pro-caspase-1, converting IL-1β and IL-18 to their mature forms, and promoting pyroptosis by converting Gasdermin-D to GSDMD-N fragments. It is involved in multiple biological processes and immune-related pathways, playing a crucial role in host defense and immunity [1,2].

In B cells, conditional knockout of Aim2 in a pristane-induced mouse model of lupus reduces the frequency of CD19+ B-cells, dampens antibody production, and attenuates lupus symptoms. This indicates that Aim2 in B cells promotes B-cell differentiation by modulating the Bcl-6-Blimp-1 axis, providing a potential target for SLE treatment [3]. In rhabdomyolysis-induced acute kidney injury mouse models, Aim2-deficiency leads to massive macrophage accumulation, delayed functional recovery, and perpetuating fibrosis in the kidney, as well as accelerated aberrant inflammation, suggesting that dsDNA-induced Aim2 pyroptosis in macrophages halts aberrant inflammation during this injury [5]. In renal cell carcinoma, Aim2 promotes cancer progression and sunitinib resistance in an inflammasome-independent manner through the FOXO3a-ACSL4 axis-regulated ferroptosis, offering new therapeutic targets for RCC diagnosis and treatment [4].

In conclusion, Aim2 plays essential roles in innate immunity, inflammation, and cell death processes. Gene knockout mouse models have revealed its significance in diseases such as systemic lupus erythematosus, rhabdomyolysis-induced acute kidney injury, and renal cell carcinoma. These findings enhance our understanding of Aim2's functions and provide potential therapeutic directions for related diseases.

References:

1. Du, Luping, Wang, Xuyang, Chen, Siyuan, Guo, Xiaogang. 2022. The AIM2 inflammasome: A novel biomarker and target in cardiovascular disease. In Pharmacological research, 186, 106533. doi:10.1016/j.phrs.2022.106533. https://pubmed.ncbi.nlm.nih.gov/36332811/

2. Wang, Bing, Tian, Yuan, Yin, Qian. . AIM2 Inflammasome Assembly and Signaling. In Advances in experimental medicine and biology, 1172, 143-155. doi:10.1007/978-981-13-9367-9_7. https://pubmed.ncbi.nlm.nih.gov/31628655/

3. Yang, Ming, Long, Di, Hu, Longyuan, Wu, Haijing, Lu, Qianjin. 2021. AIM2 deficiency in B cells ameliorates systemic lupus erythematosus by regulating Blimp-1-Bcl-6 axis-mediated B-cell differentiation. In Signal transduction and targeted therapy, 6, 341. doi:10.1038/s41392-021-00725-x. https://pubmed.ncbi.nlm.nih.gov/34521812/

4. Wang, Qi, Gao, Su, Shou, Yi, Xu, Tianbo, Zhang, Xiaoping. 2023. AIM2 promotes renal cell carcinoma progression and sunitinib resistance through FOXO3a-ACSL4 axis-regulated ferroptosis. In International journal of biological sciences, 19, 1266-1283. doi:10.7150/ijbs.79853. https://pubmed.ncbi.nlm.nih.gov/36923928/

5. Baatarjav, Chintogtokh, Komada, Takanori, Karasawa, Tadayoshi, Matsumura, Takayoshi, Takahashi, Masafumi. 2022. dsDNA-induced AIM2 pyroptosis halts aberrant inflammation during rhabdomyolysis-induced acute kidney injury. In Cell death and differentiation, 29, 2487-2502. doi:10.1038/s41418-022-01033-9. https://pubmed.ncbi.nlm.nih.gov/35739254/