Cargando…
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...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728011/ https://www.ncbi.nlm.nih.gov/pubmed/35003105 http://dx.doi.org/10.3389/fimmu.2021.786595 |
_version_ | 1784626637576339456 |
---|---|
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 |
author_facet | 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 |
author_sort | Kobayashi, Daichi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8728011 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87280112022-01-06 Extracellular ATP Limits Homeostatic T Cell Migration Within Lymph Nodes 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 Front Immunol Immunology 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. Frontiers Media S.A. 2021-12-22 /pmc/articles/PMC8728011/ /pubmed/35003105 http://dx.doi.org/10.3389/fimmu.2021.786595 Text en Copyright © 2021 Kobayashi, Sugiura, Umemoto, Takeda, Ueta, Hayasaka, Matsuzaki, Katakai, Suematsu, Hamachi, Yegutkin, Salmi, Jalkanen and Miyasaka https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology 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 Extracellular ATP Limits Homeostatic T Cell Migration Within Lymph Nodes |
title | Extracellular ATP Limits Homeostatic T Cell Migration Within Lymph Nodes |
title_full | Extracellular ATP Limits Homeostatic T Cell Migration Within Lymph Nodes |
title_fullStr | Extracellular ATP Limits Homeostatic T Cell Migration Within Lymph Nodes |
title_full_unstemmed | Extracellular ATP Limits Homeostatic T Cell Migration Within Lymph Nodes |
title_short | Extracellular ATP Limits Homeostatic T Cell Migration Within Lymph Nodes |
title_sort | extracellular atp limits homeostatic t cell migration within lymph nodes |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728011/ https://www.ncbi.nlm.nih.gov/pubmed/35003105 http://dx.doi.org/10.3389/fimmu.2021.786595 |
work_keys_str_mv | AT kobayashidaichi extracellularatplimitshomeostatictcellmigrationwithinlymphnodes AT sugiurayuki extracellularatplimitshomeostatictcellmigrationwithinlymphnodes AT umemotoeiji extracellularatplimitshomeostatictcellmigrationwithinlymphnodes AT takedaakira extracellularatplimitshomeostatictcellmigrationwithinlymphnodes AT uetahisashi extracellularatplimitshomeostatictcellmigrationwithinlymphnodes AT hayasakaharuko extracellularatplimitshomeostatictcellmigrationwithinlymphnodes AT matsuzakishinsuke extracellularatplimitshomeostatictcellmigrationwithinlymphnodes AT katakaitomoya extracellularatplimitshomeostatictcellmigrationwithinlymphnodes AT suematsumakoto extracellularatplimitshomeostatictcellmigrationwithinlymphnodes AT hamachiitaru extracellularatplimitshomeostatictcellmigrationwithinlymphnodes AT yegutkingennadyg extracellularatplimitshomeostatictcellmigrationwithinlymphnodes AT salmimarko extracellularatplimitshomeostatictcellmigrationwithinlymphnodes AT jalkanensirpa extracellularatplimitshomeostatictcellmigrationwithinlymphnodes AT miyasakamasayuki extracellularatplimitshomeostatictcellmigrationwithinlymphnodes |