Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 4, Pages -Publisher
MDPI
DOI: 10.3390/ijms23042230
Keywords
absent in melanoma 2; AIM2; inflammasome; T cell; CD4(+); regulatory T cell; Treg; FOXP3
Funding
- FEDER funds [PI16/01833, PI19/01554]
- Instituto Nacional de Salud Carlos III (Ministerio de Ciencia e Innovacion, Madrid, Spain)
- Conselleria de Santitat de la Generalitat Valenciana (Valencia, Spain) [CDEI-03/20-A]
- Generalitat Valenciana (Valencia, Spain) [PROMETEO/2021/0033]
- Agencia Estatal de Investigacion (Ministerio de Ciencia e Innovacion, Madrid, Spain) [PID2019-107036RB-IOO]
- La Caixa Foundation [100010434, LCF/BQ/DI21/11860047]
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This study demonstrates that AIM2 is not only important in innate immune cells but also plays a crucial role in CD4(+) T cells, specifically in the differentiation and function of regulatory T cells (Tregs).
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. Naive 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(-/-)-naive 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.
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