Extracellular ATP Limits Homeostatic T Cell Migration Within Lymph Nodes

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.

• Publication year

  2021

• Venue

  Frontiers in Immunology

• Publication date

  2021-12-22

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3389/fimmu.2021.786595PMID 35003105PMCID 8728011
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2018influential reference
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  2004cited by this paper
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  2003cited by this paper
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  2001cited by this paper
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  2000cited by this paper
• CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs.

  1999influential reference
• In situ analysis of lymphocyte migration to lymph nodes.

  1998cited by this paper
• The influence of afferent lymphatic vessel interruption on vascular addressin expression

  1991cited by this paper
• Disappearance and reappearance of high endothelial venules and immigrating lymphocytes in lymph nodes deprived of afferent lymphatic vessels: a possible regulatory role of macrophages in lymphocyte migration

  1983cited by this paper
• Small lymphocytes in peripheral lymphoid tissues of nude mice. Life-span and distribution.

  1975cited by this paper
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  year unknowncited by this paper

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