Approximately 358 million individuals worldwide are affected by asthma, a prevalent respiratory condition that can affect both children and adults [1]. The characteristic features of asthma include airway inflammation, swelling of the airway mucosa, excessive mucus secretion, and recurrent bronchospasms [2]. Although inhalation of corticosteroids (ICS) or ICS/long-acting beta-agonist (LABA) combination therapy can help asthma patients avoid exacerbations, there remains a possibility of acute asthma attacks and a decline in disease management for certain individuals [3], [4]. Reports indicate that approximately 2 million emergency visits and 500,000 hospitalizations occur in the United States annually as a result of acute asthma episodes [5]. Additionally, approximately 25 % of asthma patients in the US need to be hospitalized due to these sudden attacks [5]. Therefore, exploring new therapeutic strategies can be beneficial in gaining a deeper comprehension of the molecular mechanism underlying asthma.

Inflammasomes are molecular complexes that activate inflammatory responses and play a critical role in the innate immune system's response to pathogen- or damage-associated molecular patterns (PAMPs or DAMPs) [6]. Activation of the NLRP3 inflammasome is also involved in inflammation caused by allergens in the respiratory tract. Reports suggest that there is a notable increase in the expression of NLRP3 in individuals suffering from severe asthma, which contributes to the development of Th2-type airway reactions [7], [8]. Additionally, CD4 + T cells express NLRP3 and interact with the Il4 promoter, working together with the transcription factor IRF4 to activate its transcription [9]. This specifically promotes a TH2 transcriptional program in a self-contained manner within the cell [9]. Therefore, understanding how inflammasomes regulate immune responses and contribute to disease pathogenesis is essential for developing more effective therapeutic strategies for managing asthma and improving patients' quality of life.

Trim27, a member of the TRIM (tripartite motif-containing) family, plays a crucial role in the immune system and regulation of inflammation through its ability to identify proteins for ubiquitination [10]. For instance, Trim27 has been shown to facilitate the initiation of the nuclear factor-κB (NF-κB) signaling pathway by ubiquitinating IκBα (an inhibitor of NF-κB alpha) [11]. Through its interaction with TBK1, Trim27 promotes its ubiquitination, leading to proteasomal degradation and subsequent decrease in type I IFN production [12], [13], [14]. Additionally, Trim27 can engage with NOD2, initiating its ubiquitination through K48-linked ubiquitin chains, resulting in proteasomal degradation [15]. This interaction may influence proinflammatory responses mediated by NOD2 and contribute to the development of Crohn's disease [15]. Although Trim27 has been associated with various disorders such as cancer, cardiac hypertrophy, ischemia–reperfusion injury, and Parkinson's disease [10], its connection to asthma has not been previously reported.

The current treatment of asthma, although effective in relieving the airway inflammation, still faces significant gaps that limit its overall efficacy. One such gap is the limited ability to target the underlying mechanisms of the disease, particularly in the early stages. Trim27 holds the promise of addressing these gaps due to its importance in regulation of inflammatory response [11], [12], [13], [14], [15]. By specifically targeting Trim27 in the early stages of asthma, there is the potential to halt the progression of the disease and prevent the development of chronic symptoms. This study found an increased Trim27 expression in the airway epithelium of mice with asthma, and silencing its expression offers protection from airway inflammation and oxidative stress in these mice. Additionally, we revealed that NLRP3 inflammasome activation was enhanced by Trim27 both in vitro and in vivo. Our findings also demonstrated that the ubiquitin ligase activity of Trim27 contributes to its involvement in asthma and inflammasome activation. The findings suggest that Trim27 could potentially serve as an effective therapeutic target for the treatment of asthma.