Loss of WDFY3 ameliorates severity of serum transfer-induced arthritis independently of autophagy

Dennis J. Wu, Iannis Adamopoulos

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

WDFY3 is a master regulator of selective autophagy that we recently showed to interact with TRAF6 and augment RANKL-induced osteoclastogenesis in vitro and in vivo via the NF-κB pathway. Since the NF-κB pathway plays a major role in inflammation herein, we investigate the role of WDFY3 in an arthritis animal model. Our data show that WDFY3 conditional knockout mice (Wdfy3loxP/loxP-LysM-Cre+) were protected in the K/BxN serum transfer-induced arthritis animal model. These effects were independent of alterations in starvation-induced autophagy as evidenced by Western blot analysis of the autophagy marker LC3, autophagosome formation in osteoclast precursors and lysosome formation in osteoclasts derived from WDFY3-cKO mice compared to controls. Moreover, we demonstrate by immunofluorescence and co-immunoprecipitation that WDFY3 interacts with SQSTM1 in macrophages and osteoclasts. Collectively, our data suggest that loss of WDFY3 in myeloid cells leads to reduced severity of inflammatory arthritis independently of WDFY3 function in starvation-induced autophagy.

Original languageEnglish (US)
Pages (from-to)61-69
Number of pages9
JournalCellular Immunology
Volume316
DOIs
StatePublished - Jun 1 2017

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Autophagy
Arthritis
Osteoclasts
Starvation
Serum
Animal Models
TNF Receptor-Associated Factor 6
Myeloid Cells
Lysosomes
Immunoprecipitation
Osteogenesis
Knockout Mice
Fluorescent Antibody Technique
Western Blotting
Macrophages
Inflammation

Keywords

  • ALFY
  • Autophagy
  • Autophagy-linked FYVE containing protein
  • Musculoskeletal diseases
  • Osteoclast
  • WDFY3

ASJC Scopus subject areas

  • Immunology

Cite this

Loss of WDFY3 ameliorates severity of serum transfer-induced arthritis independently of autophagy. / Wu, Dennis J.; Adamopoulos, Iannis.

In: Cellular Immunology, Vol. 316, 01.06.2017, p. 61-69.

Research output: Contribution to journalArticle

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