Absent in melanoma 2 (AIM2) in rheumatoid arthritis: novel molecular insights and implications

Absent in melanoma 2 (AIM2), a member of the Pyrin and HIN domain protein family, is a cytoplasmic receptor that recognizes double-stranded DNA. AIM2 exhibits limited expression under physiological conditions but is widely expressed in many human diseases, including autoimmune diseases, and plays an essential role in the immune response. Rheumatoid arthritis (RA) is an autoimmune disease that poses a severe threat to physical and mental health, and is caused by several genetic and metabolic factors. Multiple immune cells interact to form a complex inflammatory network that mediates inflammatory responses and bone destruction. Abnormal AIM2 expression in multiple immune cell populations (T cells, B cells, fibroblast-like synoviocytes, monocytes, and macrophages) may regulate multiple functional responses in RA through mechanisms such as pyroptosis, PANoptosis, and regulation of other molecules. In this review, we describe and summarize the functional regulation and impact of AIM2 expression in immune cells to improve our understanding of the complex pathological mechanisms. These insights may provide potential directions for the development of new clinical diagnostic strategies for RA.