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Human adenosine deaminases ADA1 and ADA2 bind to different subsets of immune cells

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Abstract

At sites of inflammation and tumor growth, the local concentration of extracellular adenosine rapidly increases and plays a role in controlling the immune responses of nearby cells. Adenosine deaminases ADA1 and ADA2 (ADAs) decrease the level of adenosine by converting it to inosine, which serves as a negative feedback mechanism. Mutations in the genes encoding ADAs lead to impaired immune function, which suggests a crucial role for ADAs in immune system regulation. It is not clear why humans and other mammals possess two enzymes with adenosine deaminase activity. Here, we found that ADA2 binds to neutrophils, monocytes, NK cells and B cells that do not express CD26, a receptor for ADA1. Moreover, the analysis of CD4+ T-cell subset revealed that ADA2 specifically binds to regulatory T cells expressing CD39 and lacking the receptor for ADA1. Also, it was found that ADA1 binds to CD16− monocytes, while CD16+ monocytes preferably bind ADA2. A study of the blood samples from ADA2-deficient patients showed a dramatic reduction in the number of lymphocyte subsets and an increased concentration of TNF-α in plasma. Our results suggest the existence of a new mechanism, where the activation and survival of immune cells is regulated through the activities of ADA2 or ADA1 anchored to the cell surface.

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Acknowledgments

This study was supported by a Grant 256053 from the Finnish Academy to A.Z.

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    Authors and Affiliations

    1. Guangzhou Women and Children’s Medical Center, Guangzhou Institute of Pediatrics, 9 Jinsui Road, Tianhe, Guangzhou, 510623, Guangdong, China

      Yuliia Kaljas, Chengqian Liu, Maksym Skaldin & Andrey V. Zavialov

    2. Turku Centre for Biotechnology, University of Turku, Tykistokatu 6, 20520, Turku, Finland

      Yuliia Kaljas, Chengqian Liu, Maksym Skaldin & Andrey V. Zavialov

    3. National Institutes of Health, National Human Genome Research Institute, Bldg. 10, Bethesda, MD, 20892, USA

      Qing Zhou

    4. Department of Public Health, John A. Burns School of Medicine, University of Hawaii at Manoa, 1960 East West Road, Biomed, Honolulu, HI, 96822, USA

      Chengxiang Wu, Yuanan Lu & Ivona Aksentijevich

    5. Division of Regenerative Medicine, Tulane National Primate Research Center, 18703 Three River Road, Covington, LA, 70433, USA

      Chengxiang Wu

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    1. Yuliia Kaljas
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    Kaljas, Y., Liu, C., Skaldin, M. et al. Human adenosine deaminases ADA1 and ADA2 bind to different subsets of immune cells. Cell. Mol. Life Sci. 74, 555–570 (2017). https://doi.org/10.1007/s00018-016-2357-0

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