AUTHOR=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 TITLE=Extracellular ATP Limits Homeostatic T Cell Migration Within Lymph Nodes JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.786595 DOI=10.3389/fimmu.2021.786595 ISSN=1664-3224 ABSTRACT=

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.