Evidence map›Paper›PMID 23455504›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2013

Orai1 function is essential for T cell homing to lymph nodes.

Milton L Greenberg, Ying Yu, Sabrina Leverrier, Shenyuan L Zhang, Ian Parker, Michael D Cahalan

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.4field-weighted citation impact, top 22% 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

18 citing papers in PubMed, 27 citations in OpenAlex.

  1. Trial
  2. CRAC channels as targets for immunotherapy.Current opinion in immunology · 2026
    Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Intermittent CaeLife · 2017
    Article
  12. Article
  13. Article
  14. Genetically targeted single-channel optical recording reveals multiple Orai1 gating states and oscillations in calcium influx.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  15. Review
  16. Ion channels in innate and adaptive immunity.Annual review of immunology · 2015
    Review
  17. Article
  18. Article
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

6 authors at 1 institution in 1 country.

Milton L GreenbergDepartment of Physiology and Biophysics, University of California Irvine, Irvine, CA 92697, USA.
Ying Yu
Sabrina Leverrier
Shenyuan L Zhang
Ian Parker
Michael D Cahalan
University of California, Irvine · US

Funding

Institute for Clinical and Translational ScienceUL1TR000153 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI COOPER, DAN M · 2012 to 2015
$12.1M
Molecular Mechanisms of lon Channels in T LymphocytesR01NS014609 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI CAHALAN, MICHAEL D · 1985 to 2022
$7.0M
Elementary Events of Intracellular Calcium SignalingR37GM048071 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI PARKER, IAN · 2011 to 2020
$5.3M
THE ROLE OF ION CHANNELS IN LYMPHOCYTE ACTIVATIONR01GM041514 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI CAHALAN, MICHAEL D · 1988 to 2013
$5.2M
SPATIAL AND TEMPORAL ASPECTS OF INSP3 SIGNALLINGR01GM048071 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI PARKER, IAN · 1992 to 2010
$3.9M
Molecular Mechanisms of Ion Channels in T LymphocytesR37NS014609 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI CAHALAN, MICHAEL D · 2006 to 2012
$3.3M
Immunology Research Training ProgramT32AI060573 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI PEARLMAN, ERIC · 2005 to 2020
$1.9M
Molecular Mechanisms of lon Channels in T LymphocytesR56NS014609 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI CAHALAN, MICHAEL D · 2018 to 2018
$514k
NCATS NIH HHS UL1 TR000153NIAID NIH HHS T32 AI060573NIAID NIH HHS T32-AI-060573NIGMS NIH HHS GM-41514NIGMS NIH HHS GM-48071NIGMS NIH HHS R01 GM041514NIGMS NIH HHS R01 GM048071NIGMS NIH HHS R37 GM048071NINDS NIH HHS NS-14609NINDS NIH HHS R01 NS014609NINDS NIH HHS R37 NS014609NINDS NIH HHS R56 NS014609
6 · The paper itself

Abstract

In T lymphocytes, Ca(2+) release-activated Ca(2+) (CRAC) channels composed of Orai1 subunits trigger Ag-induced gene expression and cell proliferation through the NFAT pathway. We evaluated the requirement of CRAC channel function for lymphocyte homing using expression of a dominant-negative Orai1-E106A mutant to suppress Ca(2+) signaling. To investigate homing and motility of human lymphocytes in immunocompromised mouse hosts, we transferred human lymphocytes either acutely or after stable engraftment after a second transfer from the same blood donor. Human and mouse lymphocyte homing was assessed, and cells were tracked within lymph nodes (LNs) by two-photon microscopy. Our results demonstrate that human T and B lymphocytes home into and migrate within the LNs of immunocompromised NOD.SCID mice similar to murine lymphocytes. Human T and B cells colocalized in atrophied or reconstituted mouse LNs, where T cells migrated in a random walk at velocities of 9-13 μm/min and B cells at 6 μm/min. Expression of Orai1-E106A inhibited CRAC channel function in human and mouse T cells, and prevented homing from high endothelial venules into murine LNs. Ca(2+) signals induced by CCL21 were also inhibited in T cells expressing Orai1-E106A. With CRAC channels inhibited, the high-affinity form of LFA-1 failed to become active, and T cells failed to migrate across endothelial cells in a transwell model. These results establish a requirement for CRAC channel-mediated Ca(2+) influx for T cell homing to LNs mediated by high-affinity integrin activation and chemokine-induced transendothelial migration.

Indexed as

AnimalsCalcium ChannelsCalcium SignalingCell MovementCell TrackingChemokine CCL21HumansImmunocompromised HostLymph NodesLymphocyte Function-Associated Antigen-1MiceMice, Inbred NODMice, SCIDMutationORAI1 ProteinT-LymphocytesCalcium ChannelsChemokine CCL21Lymphocyte Function-Associated Antigen-1ORAI1 ProteinOrai1 protein, mouse

Identifiers

PMID23455504
PMCPMC3608704
OpenAlexW2159942756

What OpenQuestion holds

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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.