Human adenosine deaminases ADA1 and ADA2 bind to different subsets of immune cells.
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.
Guangzhou Women and Children's Medical Center, Guangzhou Institute of Pediatrics, 9 Jinsui Road, Tianhe, Guangzhou, 510623, Guangdong, China.|Turku Centre for Biotechnology, University of Turku, Tykistokatu 6, 20520, Turku, Finland.
Yuliia
Y
Kaljas
Guangzhou Women and Children's Medical Center, Guangzhou Institute of Pediatrics, 9 Jinsui Road, Tianhe, Guangzhou, 510623, Guangdong, China.|Turku Centre for Biotechnology, University of Turku, Tykistokatu 6, 20520, Turku, Finland.
Chengqian
C
Liu
Guangzhou Women and Children's Medical Center, Guangzhou Institute of Pediatrics, 9 Jinsui Road, Tianhe, Guangzhou, 510623, Guangdong, China.|Turku Centre for Biotechnology, University of Turku, Tykistokatu 6, 20520, Turku, Finland.
Maksym
M
Skaldin
Department of Public Health, John A. Burns School of Medicine, University of Hawaii at Manoa, 1960 East West Road, Biomed, Honolulu, HI, 96822, USA.|Division of Regenerative Medicine, Tulane National Primate Research Center, 18703 Three River Road, Covington, LA, 70433, USA.
Chengxiang
C
Wu
National Institutes of Health, National Human Genome Research Institute, Bldg. 10, Bethesda, MD, 20892, USA.
Qing
Q
Zhou
Department of Public Health, John A. Burns School of Medicine, University of Hawaii at Manoa, 1960 East West Road, Biomed, Honolulu, HI, 96822, USA.
Yuanan
Y
Lu
Department of Public Health, John A. Burns School of Medicine, University of Hawaii at Manoa, 1960 East West Road, Biomed, Honolulu, HI, 96822, USA.
Ivona
I
Aksentijevich
Guangzhou Women and Children's Medical Center, Guangzhou Institute of Pediatrics, 9 Jinsui Road, Tianhe, Guangzhou, 510623, Guangdong, China. andrey.zavialov@gmail.com.|Turku Centre for Biotechnology, University of Turku, Tykistokatu 6, 20520, Turku, Finland. andrey.zavialov@gmail.com.
Andrey V
0000-0001-6420-0368
AV
Zavialov
D000243:Adenosine Deaminase / Q000172:deficiency / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001081:Apyrase / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000276:immunology; D022423:Myeloid Cells / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D015703:Antigens, CD; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D000243:Adenosine Deaminase; D001081:Apyrase; C067869:CD39 antigen
Adenosine; Adenosine deaminase 2 deficiency; Adenosine deaminases; Immune cells
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