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

研究成果: Article査読

抄録

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.

本文言語English
論文番号786595
ジャーナルFrontiers in Immunology
12
DOI
出版ステータスPublished - 2021 12月 22

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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