Evidence map›Paper›PMID 19342685›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2009

P2X7 receptor-stimulated secretion of MHC class II-containing exosomes requires the ASC/NLRP3 inflammasome but is independent of caspase-1.

Yan Qu, Lakshmi Ramachandra, Susanne Mohr, Luigi Franchi, Clifford V Harding, Gabriel Nunez, George R Dubyak

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed
4.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

94 citing papers in PubMed, 158 citations in OpenAlex.

  1. Article
  2. Review
  3. Adenosine triphosphate-mediated signaling of P2X7 receptors controls donor extracellular vesicle release and major histocompatibility complex cross-decoration after allotransplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025
    Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. The gasdermin family: emerging therapeutic targets in diseases.Signal transduction and targeted therapy · 2024
    Review
  11. Review
  12. Review
  13. TheFrontiers in immunology · 2024
    Article
  14. Review
  15. P2XInternational journal of molecular sciences · 2023
    Review
  16. Review
  17. Article
  18. Frontiers in immunology · 2023
    Article
  19. Review
  20. Review

34 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Yan QuDepartment of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44120, USA.
Lakshmi Ramachandra
Susanne Mohr
Luigi Franchi
Clifford V Harding
Gabriel Nunez
George R Dubyak
University of Michigan · USUniversity School · US

Funding

TRANSMEMBRANE SIGNALLING IN SMOOTH MUSCLE CELL LINESR01GM036387 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI DUBYAK, GEORGE R · 1987 to 2014
$4.5M
Cryopyrin/NLRP3 Signaling in Inflammation and Innate ImmunityR37AI063331 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NUNEZ, GABRIEL · 2016 to 2025
$3.9M
Cryopyrin Signaling in Inflammation and Innate ImmunityR01AI063331 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NUNEZ, GABRIEL · 2005 to 2015
$3.3M
CLASS II MHC TRANSPORT AND FUNCTIONR01AI035726 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI HARDING, CLIFFORD V · 1994 to 2010
$3.0M
M. tuberculosis lipoprotein-TLR2 interactionsR01AI069085 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI HARDING, CLIFFORD V · 2007 to 2011
$1.9M
Role of Ipaf in Inflammation and Host DefenseR01AI064748 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NUNEZ, GABRIEL · 2005 to 2009
$1.6M
IL-1 beta Signaling in Diabetic RetinopathyR01EY017206 · NEI · MICHIGAN STATE UNIVERSITY · PI MOHR, SUSANNE · 2006 to 2010
$1.5M
Cryopyrin/NLRP3 Signaling in Inflammation and Innate ImmunityR56AI063331 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NUNEZ, GABRIEL · 2010 to 2010
$386k
NEI NIH HHS R01 EY017206NIAID NIH HHS AI035726NIAID NIH HHS AI063331NIAID NIH HHS AI064748NIAID NIH HHS AI069085NIAID NIH HHS R01 AI035726NIAID NIH HHS R01 AI063331NIAID NIH HHS R01 AI064748NIAID NIH HHS R01 AI069085NIAID NIH HHS R37 AI063331NIAID NIH HHS R56 AI063331NIGMS NIH HHS GM36387NIGMS NIH HHS R01 GM036387
6 · The paper itself

Abstract

We recently reported that P2X7 receptor (P2X7R)-induced activation of caspase-1 inflammasomes is accompanied by release of MHC class II (MHC-II) protein into extracellular compartments during brief stimulation of murine macrophages with ATP. Here we demonstrate that MHC-II containing membranes released from macrophages or dendritic cells (DCs) in response to P2X7R stimulation comprise two pools of vesicles with distinct biogenesis: one pool comprises 100- to 600-nm microvesicles derived from direct budding of the plasma membrane, while the second pool is composed of 50- to 80-nm exosomes released from multivesicular bodies. ATP-stimulated release of MHC-II in these membrane fractions is observed within 15 min and results in the export of approximately 15% of the total MHC-II pool within 90 min. ATP did not stimulate MHC-II release in macrophages from P2X7R knockout mice. The inflammasome regulatory proteins, ASC (apoptosis-associated speck-like protein containing a caspase-recruitment domain) and NLRP3 (NLR family, pyrin domain containing 3), which are essential for caspase-1 activation, were also required for the P2X7R-regulated release of the exosome but not the microvesicle MHC-II pool. Treatment of bone marrow-derived macrophages with YVAD-cmk, a peptide inhibitor of caspase-1, also abrogated P2X7R-dependent MHC-II secretion. Surprisingly, however, MHC-II release in response to ATP was intact in caspase-1(-/-) macrophages. The inhibitory actions of YVAD-cmk were mimicked by the pan-caspase inhibitor zVAD-fmk and the serine protease inhibitor TPCK, but not the caspase-3 inhibitor DEVD-cho. These data suggest that the ASC/NLRP3 inflammasome complexes assembled in response to P2X7R activation involve protease effector(s) in addition to caspase-1, and that these proteases may play important roles in regulating the membrane trafficking pathways that control biogenesis and release of MHC-II-containing exosomes.

Indexed as

Adenosine TriphosphateAnimalsApoptosis Regulatory ProteinsCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1Cell DifferentiationCells, CulturedCytoskeletal ProteinsDendritic CellsExosomesHistocompatibility Antigens Class IIMacrophagesMiceMice, Inbred C57BLMice, KnockoutAdenosine TriphosphateApoptosis Regulatory ProteinsCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1Cytoskeletal ProteinsHistocompatibility Antigens Class IINLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseP2rx7 protein, mousePycard protein, mouseReceptors, Purinergic P2Receptors, Purinergic P2X7

Identifiers

PMID19342685
PMCPMC2768485
OpenAlexW1604448976

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.