Pattern recognition receptor AIM2: Activation, regulation and the role in transplant immunology

Abstract

<p indent="0mm">Pattern recognition receptors (PRRs), expressed by innate immune cells, serve as safety indicators by recognizing various danger signals. In transplant immunology, damage-associated molecular patterns (DAMPs) released after cell injury are identified by PRRs, leading to an enhanced inflammatory response and transplant rejection. Absent in melanoma 2 (AIM2) is a pattern recognition receptor located in the cytoplasm that is specialized in recognizing abnormal dsDNA in the cytoplasm and significantly regulates immune responses. Abnormal activation of AIM2 leads to excessive inflammatory response and immune dysregulation. The important regulatory role of PRRs in transplant immunology has been revealed, but literature summarizing and analyzing the regulatory role of AIM2 in transplant immunology has not been fully elucidated yet. AIM2, expressed in antigen-presenting cells, plays a major role in recognizing endogenous dsDNA. Antigen-presenting cells identify dsDNA from the nucleus and mitochondria through phagocytosis as well as the exosomal pathway. In the first part of this paper, we familiarized the various ways of donor-derived cell-free DNA (dd-cfDNA) recognition by AIM2, and we also analyzed the key steps in the activation process of AIM2. Inappropriate activation of AIM2 can lead to excessive inflammatory responses and cause various immune-related diseases. The regulation of AIM2 activation is essential to maintain the balance of cellular physiological activities. In the second part, this paper analyzes the multiple levels of regulation of AIM2 to provide a theoretical basis for further study of AIM2 pathway activation. This study discusses the role of AIM2 in transplant immunology in terms of innate and adaptive immune systems. Activation of the innate immune system and the inflammatory response plays an integral role in initiating and maintaining the adaptive immune response. The recognition of dsDNA by AIM2 activates intrinsic immune cells and enhances the inflammatory environment in the graft via the inflammasome pathway, which may play a key role in the influence of AIM2 on transplant rejection. Most studies on PRRs have focused on intrinsic immune cells, and few studies have on AIM2 regulation of the adaptive immune system. However, present findings suggest that AIM2 is an important regulator of Treg cell differentiation and can maintain Treg cell stability, and that AIM2 is involved in regulating B cells through a variety of pathways. In conclusion, there was a significant association between AIM2 activation and the severity of transplant rejection. Previous studies have shown that AIM2 is involved in regulating the differentiation and stability of dendritic, Treg, and B cells. AIM2 is involved in the regulation of the immune tolerance induction by MDSCs. Inflammasomes and multiple independent pathways are involved in AIM2 regulation of immune rejection, but the specific mechanism is still unknown. This study innovatively analyzes and summarizes the role of AIM2 in transplant immunology, which can help researchers in related fields to further understand the relationship between the pattern recognition receptor AIM2 and transplant immunology and provide new ideas for exploring the induction of immune tolerance.