Dendritic cells utilize the evolutionarily conserved WASH and retromer complexes to promote MHCII recycling and helper T cell priming

Daniel B. Graham, Douglas G. Osborne, Joshua T. Piotrowski, Timothy S. Gomez, Grzegorz B. Gmyrek, Holly M. Akilesh, Adish Dani, Daniel D Billadeau, Wojciech Swat

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Immature dendritic cells (DCs) maintain a highly dynamic pool of recycling MHCII that promotes sampling of environmental antigens for presentation to T helper cells. However, the molecular basis of MHCII recycling and the cellular machinery that orchestrates MHCII trafficking are incompletely understood. Using a mouse model we show that WASH, an actin regulatory protein that facilitates retromer function, is essential for MHCII recycling and efficient priming of T helper cells. We further demonstrate that WASH deficiency results in impaired MHCII surface levels, recycling, and an accumulation of polyubiquitinated MHCII complexes, which are subsequently slated for premature lysosomal degradation. Consequently, conditional deletion of the Wash gene in DCs impairs priming of both conventional and autoimmune T helper cells in vivo and attenuates disease progression in a model of experimental autoimmune encephalitis (EAE). Thus, we identify a novel mechanism in which DCs employ the evolutionarily conserved WASH and retromer complex for MHCII recycling in order to regulate T helper cell priming.

Original languageEnglish (US)
Article numbere98606
JournalPLoS One
Volume9
Issue number6
DOIs
StatePublished - Jun 2 2014

Fingerprint

T-cells
Recycling
dendritic cells
Helper-Inducer T-Lymphocytes
Dendritic Cells
recycling
T-lymphocytes
antigen presentation
gene deletion
regulatory proteins
Gene Deletion
Antigen Presentation
encephalitis
disease course
Machinery
actin
Disease Progression
Actins
Theoretical Models
Genes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Graham, D. B., Osborne, D. G., Piotrowski, J. T., Gomez, T. S., Gmyrek, G. B., Akilesh, H. M., ... Swat, W. (2014). Dendritic cells utilize the evolutionarily conserved WASH and retromer complexes to promote MHCII recycling and helper T cell priming. PLoS One, 9(6), [e98606]. https://doi.org/10.1371/journal.pone.0098606

Dendritic cells utilize the evolutionarily conserved WASH and retromer complexes to promote MHCII recycling and helper T cell priming. / Graham, Daniel B.; Osborne, Douglas G.; Piotrowski, Joshua T.; Gomez, Timothy S.; Gmyrek, Grzegorz B.; Akilesh, Holly M.; Dani, Adish; Billadeau, Daniel D; Swat, Wojciech.

In: PLoS One, Vol. 9, No. 6, e98606, 02.06.2014.

Research output: Contribution to journalArticle

Graham, Daniel B. ; Osborne, Douglas G. ; Piotrowski, Joshua T. ; Gomez, Timothy S. ; Gmyrek, Grzegorz B. ; Akilesh, Holly M. ; Dani, Adish ; Billadeau, Daniel D ; Swat, Wojciech. / Dendritic cells utilize the evolutionarily conserved WASH and retromer complexes to promote MHCII recycling and helper T cell priming. In: PLoS One. 2014 ; Vol. 9, No. 6.
@article{2a3ad69894d5415da12cf93e03c77931,
title = "Dendritic cells utilize the evolutionarily conserved WASH and retromer complexes to promote MHCII recycling and helper T cell priming",
abstract = "Immature dendritic cells (DCs) maintain a highly dynamic pool of recycling MHCII that promotes sampling of environmental antigens for presentation to T helper cells. However, the molecular basis of MHCII recycling and the cellular machinery that orchestrates MHCII trafficking are incompletely understood. Using a mouse model we show that WASH, an actin regulatory protein that facilitates retromer function, is essential for MHCII recycling and efficient priming of T helper cells. We further demonstrate that WASH deficiency results in impaired MHCII surface levels, recycling, and an accumulation of polyubiquitinated MHCII complexes, which are subsequently slated for premature lysosomal degradation. Consequently, conditional deletion of the Wash gene in DCs impairs priming of both conventional and autoimmune T helper cells in vivo and attenuates disease progression in a model of experimental autoimmune encephalitis (EAE). Thus, we identify a novel mechanism in which DCs employ the evolutionarily conserved WASH and retromer complex for MHCII recycling in order to regulate T helper cell priming.",
author = "Graham, {Daniel B.} and Osborne, {Douglas G.} and Piotrowski, {Joshua T.} and Gomez, {Timothy S.} and Gmyrek, {Grzegorz B.} and Akilesh, {Holly M.} and Adish Dani and Billadeau, {Daniel D} and Wojciech Swat",
year = "2014",
month = "6",
day = "2",
doi = "10.1371/journal.pone.0098606",
language = "English (US)",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "6",

}

TY - JOUR

T1 - Dendritic cells utilize the evolutionarily conserved WASH and retromer complexes to promote MHCII recycling and helper T cell priming

AU - Graham, Daniel B.

AU - Osborne, Douglas G.

AU - Piotrowski, Joshua T.

AU - Gomez, Timothy S.

AU - Gmyrek, Grzegorz B.

AU - Akilesh, Holly M.

AU - Dani, Adish

AU - Billadeau, Daniel D

AU - Swat, Wojciech

PY - 2014/6/2

Y1 - 2014/6/2

N2 - Immature dendritic cells (DCs) maintain a highly dynamic pool of recycling MHCII that promotes sampling of environmental antigens for presentation to T helper cells. However, the molecular basis of MHCII recycling and the cellular machinery that orchestrates MHCII trafficking are incompletely understood. Using a mouse model we show that WASH, an actin regulatory protein that facilitates retromer function, is essential for MHCII recycling and efficient priming of T helper cells. We further demonstrate that WASH deficiency results in impaired MHCII surface levels, recycling, and an accumulation of polyubiquitinated MHCII complexes, which are subsequently slated for premature lysosomal degradation. Consequently, conditional deletion of the Wash gene in DCs impairs priming of both conventional and autoimmune T helper cells in vivo and attenuates disease progression in a model of experimental autoimmune encephalitis (EAE). Thus, we identify a novel mechanism in which DCs employ the evolutionarily conserved WASH and retromer complex for MHCII recycling in order to regulate T helper cell priming.

AB - Immature dendritic cells (DCs) maintain a highly dynamic pool of recycling MHCII that promotes sampling of environmental antigens for presentation to T helper cells. However, the molecular basis of MHCII recycling and the cellular machinery that orchestrates MHCII trafficking are incompletely understood. Using a mouse model we show that WASH, an actin regulatory protein that facilitates retromer function, is essential for MHCII recycling and efficient priming of T helper cells. We further demonstrate that WASH deficiency results in impaired MHCII surface levels, recycling, and an accumulation of polyubiquitinated MHCII complexes, which are subsequently slated for premature lysosomal degradation. Consequently, conditional deletion of the Wash gene in DCs impairs priming of both conventional and autoimmune T helper cells in vivo and attenuates disease progression in a model of experimental autoimmune encephalitis (EAE). Thus, we identify a novel mechanism in which DCs employ the evolutionarily conserved WASH and retromer complex for MHCII recycling in order to regulate T helper cell priming.

UR - http://www.scopus.com/inward/record.url?scp=84902322685&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902322685&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0098606

DO - 10.1371/journal.pone.0098606

M3 - Article

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 6

M1 - e98606

ER -