Journal article
ADAR1-mediated RNA editing is required for thymic self-tolerance and inhibition of autoimmunity
T Nakahama, Y Kato, JI Kim, T Vongpipatana, Y Suzuki, CR Walkley, Y Kawahara
EMBO Reports | Published : 2018
Abstract
T cells play a crucial role in the adaptive immune system, and their maturation process is tightly regulated. Adenosine deaminase acting on RNA 1 (ADAR1) is the enzyme responsible for adenosine-to-inosine RNA editing in dsRNAs, and loss of ADAR1 activates the innate immune sensing response via melanoma differentiation-associated protein 5 (MDA5), which interprets unedited dsRNA as non-self. Although ADAR1 is highly expressed in the thymus, its role in the adaptive immune system, especially in T cells, remains elusive. Here, we demonstrate that T cell-specific deletion of Adar1 in mice causes abnormal thymic T cell maturation including impaired negative selection and autoimmunity such as spon..
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Awarded by Takeda Science Foundation
Funding Acknowledgements
We thank Drs. K. Nishikura (The Wistar Institute) and O. Takeuchi (Kyoto University) for providing A1<SUP>fl/fl</SUP> mice and Cd4<SUP>cre</SUP> mice, respectively. We thank Drs K. Takeda, H. Kayama, and I. Chinen for technical advice and all the staff in the Center for Medical Research and Education, Graduate School of Medicine, Osaka University, for technical support. Computations were partially performed on the NIG Supercomputer at ROIS National Institute of Genetics, Japan. This work was supported by Grants-in-Aid KAKENHI (25293201, 25110719, and 16H06279 to Y. Kawahara; 18K15186, 16H06279, 15K19126, and 255768 to T.N.; and 18K11526 and 15K00401 to Y. Kato) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan and by grants from the Takeda Science Foundation, the SENSHIN Medical Research Foundation, and the Mochida Memorial Foundation for Medical and Pharmaceutical Research (to Y. Kawahara), Nagao Memorial Fund (to T.N.), and Victorian Cancer Agency Mid-Career Fellowship (to C.R.W.).