Absent in Melanoma 2 (AIM2) Regulates the Stability of Regulatory T Cells

Abstract

Absent in melanoma 2 (AIM2) is a cytosolic dsDNA sensor that has been broadly studied for its role in inflammasome assembly. However, little is known about the function of AIM2 in adaptive immune cells. The purpose of this study was to investigate whether AIM2 has a cell-intrinsic role in CD4+ T cell differentiation or function. We found that AIM2 is expressed in both human and mouse CD4+ T cells and that its expression is affected by T cell receptor (TCR) activation. Naïve CD4+ T cells from AIM2-deficient (Aim2−/−) mice showed higher ability to maintain forkhead box P3 (FOXP3) expression in vitro, while their capacity to differentiate into T helper (Th)1, Th2 or Th17 cells remained unaltered. Transcriptional profiling by RNA sequencing showed that AIM2 might affect regulatory T cell (Treg) stability not by controlling the expression of Treg signature genes, but through the regulation of the cell’s metabolism. In addition, in a T cell transfer model of colitis, Aim2−/−-naïve T cells induced less severe body weight loss and displayed a higher ability to differentiate into FOXP3+ cells in vivo. In conclusion, we show that AIM2 function is not confined to innate immune cells but is also important in CD4+ T cells. Our data identify AIM2 as a regulator of FOXP3+ Treg cell differentiation and as a potential intervention target for restoring T cell homeostasis.

Aged lipid‐laden microglia display impaired responses to stroke

“…Analyses were performed as previously reported (Lozano‐Ruiz et al , 2022 ). In brief, raw reads were analyzed for data quality using FastQC v0.11.5 (Babraham Bioinformatics) and filtered using skewer v0.2.2 (Jiang et al , 2014 ) for removing the low‐quality reads and trimming the Illumina adapter.…”

AIM2 promotes TH17 cells differentiation by regulating RORγt transcription activity

“…It was already observed that the methylation and gene expression of AIM2 in memory CD4 + T cells is significantly increased when compared to naive T cells. 10 Recent studies have demonstrated that AIM2 is important for the differentiation of Treg 12 , 31 and follicular T cells (Tfh). 11 AIM2 is highly expressed in Tfh cells and positively regulates its differentiation by enhancing IL-21 production.…”

Age-dependent lipid droplet-rich microglia worsen stroke outcome in old mice

“…Analyses were performed as previously reported 61 . In brief, raw reads were analyzed for data quality using FastQC v0.11.5 (Babraham Bioinformatics) and filtered using skewer v0.2.2 62 for removing the low-quality reads and trimming the Illumina adapter.…”