Selective autophagy of the immunoproteasomes suppresses innate inflammation

ABSTRACT

Immunoproteasomes are involved in various inflammatory diseases. Upon stimulation, standard constitutive proteasomes are partially replaced by newly formed immunoproteasomes that promote inflammatory responses. How the upregulated immunoproteasomes are cleared to constrain hyper-inflammation is unknown. Recently, our studies showed that the pan-FGFR inhibitor LY2874455 efficiently activates macroautophagy/autophagy in macrophages, leading to the degradation of the immunoproteasomes. Immunoproteasome subunits are ubiquitinated and recognized by the selective autophagy receptor SQSTM1/p62. LY2874455 suppresses inflammation induced by lipopolysaccharide both in vivo and in vitro through autophagic degradation of the immunoproteasomes. In summary, our work uncovers a mechanism of inflammation suppression by autophagy in macrophages.

KEYWORDS:

• Autophagosome
• FGFR
• immunoproteasome
• inflammation
• macrophage

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Natural Science Foundation under grants 31970693 and 32022020 (to K.L.).