A1 Refereed original research article in a scientific journal
Extracellular ATP Limits Homeostatic T Cell Migration Within Lymph Nodes
Authors: Kobayashi Daichi, Sugiura Yuki, Umemoto Eiji, Takeda Akira, Ueta Hisashi, Hayasaka Haruko, Matsuzaki Shinsuke, Katakai Tomoya, Suematsu Makoto, Hamachi Itaru, Yegutkin Gennady G, Salmi Marko, Jalkanen Sirpa, Miyasaka Masayuki
Publisher: Frontiers Media SA
Publication year: 2021
Journal: Frontiers in Immunology
Journal name in source: Frontiers in immunology
Journal acronym: Front Immunol
Volume: 12
ISSN: 1664-3224
eISSN: 1664-3224
DOI: https://doi.org/10.3389/fimmu.2021.786595
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/68761676
Whereas adenosine 5'-triphosphate (ATP) is the major energy source in cells, extracellular ATP (eATP) released from activated/damaged cells is widely thought to represent a potent damage-associated molecular pattern that promotes inflammatory responses. Here, we provide suggestive evidence that eATP is constitutively produced in the uninflamed lymph node (LN) paracortex by naïve T cells responding to C-C chemokine receptor type 7 (CCR7) ligand chemokines. Consistently, eATP was markedly reduced in naïve T cell-depleted LNs, including those of nude mice, CCR7-deficient mice, and mice subjected to the interruption of the afferent lymphatics in local LNs. Stimulation with a CCR7 ligand chemokine, CCL19, induced ATP release from LN cells, which inhibited CCR7-dependent lymphocyte migration in vitro by a mechanism dependent on the purinoreceptor P2X7 (P2X7R), and P2X7R inhibition enhanced T cell retention in LNs in vivo. These results collectively indicate that paracortical eATP is produced by naïve T cells in response to constitutively expressed chemokines, and that eATP negatively regulates CCR7-mediated lymphocyte migration within LNs via a specific subtype of ATP receptor, demonstrating its fine-tuning role in homeostatic cell migration within LNs.
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