TRIM31 regulates neutrophilic asthma by suppressing IL-17 pathway through decreasing the M1-linked ubiquitination of TRAF6.

Neutrophilic asthma is defined as an inflammatory disease typified by airway neutrophil infiltration. Tripartite motif-containing protein 31 (TRIM31), an E3 ligase, is implicated in various processes, including inflammation, tumorigenesis, and immune responses. However, the function of TRIM31 in neutrophilic asthma remains to be elucidated. In the study, we identified that TRIM31 expression was markedly upregulated and interleukin 17 (IL-17) pathway had an enrichment in bronchial biopsy tissues from neutrophilic asthma patients through bioinformatics analysis. TRIM31 was also elevated in lung tissues from mice with neutrophilic asthma. Further studies revealed that TRIM31 overexpression inhibited IL-17 mediated signaling cascade. TRIM31 bonded to TRAF6 and the interaction was strengthened in a dose-dependent manner. TRIM31 overexpression reduced the total and M1-linked ubiquitin chains of TRAF6. In the presence of IL-17 A, TRIM31-TRAF6 interaction was enhanced, and TRAF6 ubiquitination further decreased. Whereas TRIM31 knockdown increased TRAF6 ubiquitination and promoted IL-17-mediated signaling activation. In addition, TRIM31 failed to regulate IL-17 signaling in the TRAF6 deficiency cells. Overall, these findings demonstrated that TRIM31 regulated inflammation in neutrophilic asthma through suppression of TRAF6-mediated IL-17 pathway. These results provided new insights into the intricate pathophysiological mechanisms of neutrophilic asthma.