Absent in Melanoma 2 (AIM2) Regulates the Stability of Regulatory T Cells.
Por:
Lozano-Ruiz B, Tzoumpa A, Martínez-Cardona C, Moreno D, Aransay AM, Cortazar AR, Picó J, Peiró G, Lozano J, Zapater P, Francés R and González-Navajas JM
Publicada:
17 feb 2022
Ahead of Print:
17 feb 2022
Resumen:
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.
Filiaciones:
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Alicante Institute for Health and Biomedical Research (ISABIAL), Hospital General Universitario Dr. Balmis, 03010 Alicante, Spain
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Alicante Institute for Health and Biomedical Research (ISABIAL), Hospital General Universitario Dr. Balmis, 03010 Alicante, Spain
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Alicante Institute for Health and Biomedical Research (ISABIAL), Hospital General Universitario Dr. Balmis, 03010 Alicante, Spain
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Alicante Institute for Health and Biomedical Research (ISABIAL), Hospital General Universitario Dr. Balmis, 03010 Alicante, Spain
Aransay AM:
Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, 28029 Madrid, Spain
Center for Cooperative Research in Biosciences (CIC bioGUNE), 48160 Derio, Spain
Cortazar AR:
Center for Cooperative Research in Biosciences (CIC bioGUNE), 48160 Derio, Spain
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Alicante Institute for Health and Biomedical Research (ISABIAL), Hospital General Universitario Dr. Balmis, 03010 Alicante, Spain
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Alicante Institute for Health and Biomedical Research (ISABIAL), Hospital General Universitario Dr. Balmis, 03010 Alicante, Spain
Pathology Unit, Hospital General Universitario Dr. Balmis, 03010 Alicante, Spain
Lozano J:
Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, 28029 Madrid, Spain
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Alicante Institute for Health and Biomedical Research (ISABIAL), Hospital General Universitario Dr. Balmis, 03010 Alicante, Spain
Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, 28029 Madrid, Spain
Department of Pharmacology, Pediatrics and Organic Chemistry, University Miguel Hernández (UMH), 03202 Elche, Spain
Institute of Research, Development and Innovation in Healthcare Biotechnology in Elche (IDiBE), University Miguel Hernández (UMH), 03202 Elche, Spain
:
Alicante Institute for Health and Biomedical Research (ISABIAL), Hospital General Universitario Dr. Balmis, 03010 Alicante, Spain
Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, 28029 Madrid, Spain
Institute of Research, Development and Innovation in Healthcare Biotechnology in Elche (IDiBE), University Miguel Hernández (UMH), 03202 Elche, Spain
Department of Clinical Medicine, University Miguel Hernández (UMH), 03202 Elche, Spain
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Alicante Institute for Health and Biomedical Research (ISABIAL), Hospital General Universitario Dr. Balmis, 03010 Alicante, Spain
Networked Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Institute of Health Carlos III, 28029 Madrid, Spain
Department of Pharmacology, Pediatrics and Organic Chemistry, University Miguel Hernández (UMH), 03202 Elche, Spain
Institute of Research, Development and Innovation in Healthcare Biotechnology in Elche (IDiBE), University Miguel Hernández (UMH), 03202 Elche, Spain
Green Published, gold
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