Extracellular ATP Limits Homeostatic T Cell Migration Within Lymph Nodes

Daichi Kobayashi, Yuki Sugiura, Eiji Umemoto, Akira Takeda, Hisashi Ueta, Haruko Hayasaka, Shinsuke Matsuzaki, Tomoya Katakai, Makoto Suematsu, Itaru Hamachi, Gennady G. Yegutkin, Marko Salmi, Sirpa Jalkanen, Masayuki Miyasaka

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number786595
JournalFrontiers in Immunology
Volume12
DOIs
Publication statusPublished - 2021 Dec 22

Keywords

  • T cells
  • adenosine 5’-triphosphate (ATP)
  • cell migration
  • chemokines
  • lymph nodes (LNs)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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