PMID- 36889584
OWN - NLM
STAT- MEDLINE
DCOM- 20230428
LR  - 20230510
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 299
IP  - 4
DP  - 2023 Apr
TI  - ATP and its metabolite adenosine cooperatively upregulate the antigen-presenting 
      molecules on dendritic cells leading to IFN-gamma production by T cells.
PG  - 104587
LID - S0021-9258(23)00229-6 [pii]
LID - 10.1016/j.jbc.2023.104587 [doi]
LID - 104587
AB  - Dendritic cells (DCs) present foreign antigens to T cells via the major 
      histocompatibility complex (MHC), thereby inducing acquired immune responses. ATP 
      accumulates at sites of inflammation or in tumor tissues, which triggers local 
      inflammatory responses. However, it remains to be clarified how ATP modulates the 
      functions of DCs. In this study, we investigated the effects of extracellular ATP 
      on mouse bone marrow-derived dendritic cells (BMDCs) as well as the potential for 
      subsequent T cell activation. We found that high concentrations of ATP (1 mM) 
      upregulated the cell surface expression levels of MHC-I, MHC-II, and 
      co-stimulatory molecules CD80 and CD86 but not those of co-inhibitory molecules 
      PD-L1 and PD-L2 in BMDCs. Increased surface expression of MHC-I, MHC-II, CD80, 
      and CD86 was inhibited by a pan-P2 receptor antagonist. In addition, the 
      upregulation of MHC-I and MHC-II expression was inhibited by an adenosine P1 
      receptor antagonist and by inhibitors of CD39 and CD73, which metabolize ATP to 
      adenosine. These results suggest that adenosine is required for the ATP-induced 
      upregulation of MHC-I and MHC-II. In the mixed leukocyte reaction assay, 
      ATP-stimulated BMDCs activated CD4 and CD8T cells and induced interferon-gamma 
      (IFN-gamma) production by these T cells. Collectively, these results suggest that 
      high concentrations of extracellular ATP upregulate the expression of 
      antigen-presenting and co-stimulatory molecules but not that of co-inhibitory 
      molecules in BMDCs. Cooperative stimulation of ATP and its metabolite adenosine 
      was required for the upregulation of MHC-I and MHC-II. These ATP-stimulated BMDCs 
      induced the activation of IFN-gamma-producing T cells upon antigen presentation.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Furuta, Kazuyuki
AU  - Furuta K
AD  - Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 
      University, Okayama, Japan. Electronic address: furutak@okayama-u.ac.jp.
FAU - Onishi, Hiroka
AU  - Onishi H
AD  - Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 
      University, Okayama, Japan.
FAU - Ikada, Yuki
AU  - Ikada Y
AD  - Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 
      University, Okayama, Japan.
FAU - Masaki, Kento
AU  - Masaki K
AD  - Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 
      University, Okayama, Japan.
FAU - Tanaka, Satoshi
AU  - Tanaka S
AD  - Department of Pharmacology, Division of Pathological Sciences, Kyoto 
      Pharmaceutical University, Kyoto, Japan.
FAU - Kaito, Chikara
AU  - Kaito C
AD  - Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 
      University, Okayama, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230306
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *T-Lymphocytes
MH  - *Dendritic Cells
MH  - Antigen Presentation
MH  - Lymphocyte Activation
MH  - Adenosine Triphosphate/metabolism
PMC - PMC10124915
OTO - NOTNLM
OT  - ATP
OT  - adenosine
OT  - antigen presentation
OT  - dendritic cell
OT  - interferon
COIS- Conflict of interest The authors declare that they have no conflicts of interest 
      with the contents of this article.
EDAT- 2023/03/09 06:00
MHDA- 2023/04/28 06:41
PMCR- 2023/03/06
CRDT- 2023/03/08 19:33
PHST- 2022/08/04 00:00 [received]
PHST- 2023/03/02 00:00 [revised]
PHST- 2023/03/03 00:00 [accepted]
PHST- 2023/04/28 06:41 [medline]
PHST- 2023/03/09 06:00 [pubmed]
PHST- 2023/03/08 19:33 [entrez]
PHST- 2023/03/06 00:00 [pmc-release]
AID - S0021-9258(23)00229-6 [pii]
AID - 104587 [pii]
AID - 10.1016/j.jbc.2023.104587 [doi]
PST - ppublish
SO  - J Biol Chem. 2023 Apr;299(4):104587. doi: 10.1016/j.jbc.2023.104587. Epub 2023 
      Mar 6.