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Defects in aminoacyl-tRNA synthetase cause partial B and T cell immunodeficiency

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Abstract

Aminoacyl-tRNA synthetases (ARSs) are emerging as important regulators in various immune diseases; however, their roles in immune cells remain unclear. In this study, using alanyl-tRNA synthetase (AARS) mutant (sti) mice with neurodegenerative disorder, we investigated the effect of translational fidelity in immune cells. Dysfunctional AARS caused disorders in immune cell responses and cellularity. The impairment was caused by dampened TCR signaling than cytokine signaling. Therefore, sti mutant inhibits TCR signaling, impeding T cell survival and responses. B cell numbers were decreased in sti mice. Despite low B cell cellularity, serum IgM, IgA, and IgE levels were higher in sti mice than in wild-type mice. Misacylation of ARS and the consequent translational infidelity induce disturbances in signaling pathways critical for immune cell survival and responses. Our findings provide a novel mechanism by which translational fidelity might play a critical role in cellular and humoral immune responses.

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Acknowledgements

We thank Dr. Lee at the KRIBB and the members of the Hong lab for critical review of this manuscript. This work was supported by the Medical Research Center Program (2015R1A5A2009656) and Basic Science Research Program (2020R1A2C1006616) through a National Research Foundation of Korea (NRF) funded by the Korean government.

Funding

Funding was provided by the Medical Research Center Program (2015R1A5A2009656) and Basic Science Research Program (2020R1A2C1006616) through a National Research Foundation of Korea (NRF).

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Author notes

  1. Ju A. Shim and Yuna Jo have contributed equally to this work.

Authors and Affiliations

  1. Department of Anatomy, Pusan National University School of Medicine, Yangsan, 50612, Republic of Korea

    Ju A. Shim, Yuna Jo, So Eun Lee, Dahyeon Ha, Jun Hwa Lee & Changwan Hong

  2. Department of Convergence Medical Science, Pusan National University School of Medicine, Yangsan, 50612, Republic of Korea

    Ju A. Shim, Yuna Jo, So Eun Lee, Dahyeon Ha, Jun Hwa Lee, Jayoung Kim, Parkyong Song, Dongjun Lee & Changwan Hong

  3. Asan Institute for Life Sciences and Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Republic of Korea

    Hyunju Hwang

  4. PNU GRAND Convergence Medical Science Education Research Center, Pusan National University School of Medicine, Yangsan, 50612, Republic of Korea

    So Eun Lee, Dahyeon Ha, Jun Hwa Lee, Jayoung Kim, Parkyong Song, Dongjun Lee & Changwan Hong

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  1. Ju A. Shim
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Contributions

CH conceived and designed the study. JAS, YJ, HH, DL, SEL, DH, JK and CH performed experiments and analyzed data. JAS, YJ, DL, JHL, PS and CH analyzed and interpreted the results. JAS and CH wrote the manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Changwan Hong.

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The authors declare no competing financial interests.

Ethical approval

All the procedures involving animals in this study complied with Pusan National University (PNU) Institutional Animal Care and Use Committee (PNU-2020-2714) and the KRIBB Animal Care and Use Committee (KRIBB-AEC-18156).

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Shim, J.A., Jo, Y., Hwang, H. et al. Defects in aminoacyl-tRNA synthetase cause partial B and T cell immunodeficiency. Cell. Mol. Life Sci. 79, 87 (2022). https://doi.org/10.1007/s00018-021-04122-z

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