Evidence map›Paper›PMID 23275443›Full record

ArticleMolecular and cellular biology2013

WASH knockout T cells demonstrate defective receptor trafficking, proliferation, and effector function.

Joshua T Piotrowski, Timothy S Gomez, Renee A Schoon, Ashutosh K Mangalam, Daniel D Billadeau

Abstract read
In one paragraph

Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
–field-weighted citation impact
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

74 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. Review

14 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

5 authors.

Joshua T PiotrowskiDepartment of Immunology, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Timothy S Gomez
Renee A Schoon
Ashutosh K Mangalam
Daniel D Billadeau

Funding

Medical Scientist Traning Program at Mayo ClinicT32GM065841 · NIGMS · MAYO CLINIC ROCHESTER · PI KAUFMANN, SCOTT H, SCHIMMENTI, LISA A · 2003 to 2022
$5.8M
Regulation of Actin Dynamics During T Cell ActivationR01AI065474 · NIAID · MAYO CLINIC ROCHESTER · PI BILLADEAU, DANIEL D · 2005 to 2014
$3.1M
NIAID NIH HHS AI065474NIAID NIH HHS R01 AI065474NIGMS NIH HHS GM065841NIGMS NIH HHS T32 GM065841
6 · The paper itself

Abstract

WASH is an Arp2/3 activator of the Wiskott-Aldrich syndrome protein superfamily that functions during endosomal trafficking processes in collaboration with the retromer and sorting nexins, but its in vivo function has not been examined. To elucidate the physiological role of WASH in T cells, we generated a WASH conditional knockout (WASHout) mouse model. Using CD4(Cre) deletion, we found that thymocyte development and naive T cell activation are unaltered in the absence of WASH. Surprisingly, despite normal T cell receptor (TCR) signaling and interleukin-2 production, WASHout T cells demonstrate significantly reduced proliferative potential and fail to effectively induce experimental autoimmune encephalomyelitis. Interestingly, after activation, WASHout T cells fail to maintain surface levels of TCR, CD28, and LFA-1. Moreover, the levels of the glucose transporter, GLUT1, are also reduced compared to wild-type T cells. We further demonstrate that the loss of surface expression of these receptors in WASHout cells results from aberrant accumulation within the collapsed endosomal compartment, ultimately leading to degradation within the lysosome. Subsequently, activated WASHout T cells experience reduced glucose uptake and metabolic output. Thus, we found that WASH is a newly recognized regulator of TCR, CD28, LFA-1, and GLUT1 endosome-to-membrane recycling. Aberrant trafficking of these key T cell proteins may potentially lead to attenuated proliferation and effector function.

Indexed as

AnimalsCD28 AntigensCD4 AntigensCell ProliferationCells, CulturedEncephalomyelitis, Autoimmune, ExperimentalGene DeletionGlucose Transporter Type 1GlycolysisInterleukin-2Lymphocyte ActivationLymphocyte Function-Associated Antigen-1MiceMice, KnockoutMicrofilament ProteinsProtein TransportCD28 AntigensCD4 AntigensGlucose Transporter Type 1Interleukin-2Lymphocyte Function-Associated Antigen-1Microfilament ProteinsReceptors, Antigen, T-CellSlc2a1 protein, mouseVesicular Transport ProteinsWASH protein, mouseWiskott-Aldrich Syndrome Protein

Identifiers

PMID23275443
PMCPMC3623087

What OpenQuestion holds

Textmetadata
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.