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

7 Scopus citations

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

ASJC Scopus subject areas

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

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    Graham, D. B., Osborne, D. G., Piotrowski, J. T., Gomez, T. S., Gmyrek, G. B., Akilesh, H. M., Dani, A., Billadeau, D. D., & 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