Aim2, also known as Absent in melanoma 2, is a cytoplasmic sensor that recognizes double-strand DNA. It is a key component of the AIM2 inflammasome, a protein platform in the cell. 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. AIM2 is involved in various biological processes related to innate immunity and inflammatory cell death [1,2,3].

In lupus, conditional knockout of Aim2 in B cells reduces the CD19+ B-cell frequency, dampens antibody production, and attenuates lupus symptoms, indicating that Aim2 promotes B-cell differentiation by modulating the Bcl-6-Blimp-1 axis [4]. In rhabdomyolysis-induced acute kidney injury, Aim2-deficiency leads to massive macrophage accumulation, delayed functional recovery, and perpetuating fibrosis in the kidney, suggesting that dsDNA-induced Aim2 pyroptosis halts aberrant inflammation [6]. In renal cell carcinoma, Aim2 promotes cancer progression and sunitinib resistance through the FOXO3a-ACSL4 axis-regulated ferroptosis in an inflammasome-independent manner [5].

In conclusion, Aim2 plays crucial roles in innate immunity, inflammation, and cell death. Studies using gene knockout (KO) or conditional knockout (CKO) mouse models have revealed its functions in diseases such as lupus, rhabdomyolysis-induced acute kidney injury, and renal cell carcinoma. These models contribute to understanding the molecular mechanisms of these diseases and potentially identifying new therapeutic targets related to Aim2.

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. Uresti-Rivera, E E, García-Hernández, M H. 2022. AIM2-inflammasome role in systemic lupus erythematous and rheumatoid arthritis. In Autoimmunity, 55, 443-454. doi:10.1080/08916934.2022.2103802. https://pubmed.ncbi.nlm.nih.gov/35880661/

4. 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/

5. 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/

6. 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/