Title: The E3 ubiquitin ligase TRIM31 attenuates NLRP3 inflammasome
activation by promoting proteasomal degradation of NLRP3

Abstract: The NLRP3 inflammasome has a fundamental role in host
defence against microbial pathogens and its deregulation may cause
diverse inflammatory diseases. NLRP3 protein expression is a
rate-limiting step for inflammasome activation, thus its expression
must be tightly controlled to maintain immune homeostasis and avoid
detrimental effects. However, how NLRP3 expression is regulated
remains largely unknown. In this study, we identify E3 ubiquitin
ligase TRIM31 as a feedback suppressor of NLRP3 inflammasome. TRIM31
directly binds to NLRP3, promotes K48-linked polyubiquitination and
proteasomal degradation of NLRP3. Consequently, TRIM31 deficiency
enhances NLRP3 inflammasome activation and aggravates alum-induced
peritonitis in vivo. Furthermore, TRIM31 deficiency attenuates the
severity of dextran sodium sulfate (DSS)-induced colitis, an
inflammatory bowel diseases model in which NLRP3 possesses protective
roles. Thus, our research describes a mechanism by which TRIM31 limits
NLRP3 inflammasome activity under physiological conditions and
suggests TRIM31 as a potential therapeutic target for the intervention
of NLRP3 inflammasome related diseases.

Figure 1: TRIM31 specifically inhibits NLRP3 inflammasome activation
Figure 2. TRIM31 promotes proteasomal degradation of NLRP3
Figure 3. TRIM31 interacts with NLRP3
Figure 4. TRIM31 promotes K48-linked polyubiquitination of NLRP3.
Figure 5. IL-1β and LPS induce TRIM31 expression
Figure 6. TRIM31 deficiency enhances IL-1β secretion and aggravates
Alum-induced peritonitis in vivo
Figure 7. TRIM31 deficiency ameliorates DSS-induced colitis
Figure 8. Working model for TRIM31 inhibiting NLRP3 inflammasome activation.
