Dendritic cell PIK3C3/VPS34 controls the pathogenicity of CNS autoimmunity independently of LC3-associated phagocytosis

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

1 Scopus Citations
View graph of relations

Author(s)

  • J. Luke Postoak
  • Wenqiang Song
  • Jennifer Martinez
  • Jianhua Zhang
  • Lan Wu
  • Luc Van Kaer

Detail(s)

Original languageEnglish
Number of pages10
Journal / PublicationAutophagy
Online published7 May 2021
Publication statusOnline published - 7 May 2021
Externally publishedYes

Abstract

PIK3C3/VPS34 is a key player in macroautophagy/autophagy and MAP1LC3/LC3-associated phagocytosis (LAP), which play critical roles in dendritic cell (DC) function. In this study, we assessed the contribution of PIK3C3 to DC function during experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). We found that Pik3c3-deficient DCs exhibit attenuated capacity to reactivate encephalitogenic T cells in the central nervous system, leading to reduced incidence and severity of EAE in DC-specific Pik3c3-deficient mice. Additionally, animals with a DC-specific deficiency in Rb1cc1/Fip200 but not Rubcn were protected against EAE, suggesting that the EAE phenotype of DC-specific Pik3c3-deficient mice is due to defective canonical autophagy rather than LAP. Collectively, our studies have revealed a critical role of PIK3C3 in DC function and the pathogenicity of these cells during EAE, with important implications for the development of immunotherapies for autoimmune diseases such as MS.

Research Area(s)

  • Autophagy, dendritic cell, experimental autoimmune encephalomyelitis, LC3-associated phagocytosis, PIK3C3/VPS34

Citation Format(s)

Dendritic cell PIK3C3/VPS34 controls the pathogenicity of CNS autoimmunity independently of LC3-associated phagocytosis. / Yang, Guan; Postoak, J. Luke; Song, Wenqiang; Martinez, Jennifer; Zhang, Jianhua; Wu, Lan; Van Kaer, Luc.

In: Autophagy, 07.05.2021.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review