The Role of TRIM24 in Allergic Rhinitis

Abstract

Allergic rhinitis (AR) is a common inflammatory disease characterized by rhinorrhea, nasal obstruction, sneezing, and itchy nose. The inflammation of nasal mucosa is ultimately caused by an exposure to allergens and immunoglobulin (Ig) E-mediated sensitization, in which T helper type 2 (Th2) cells and cytokines—interleukin (IL)-4, IL-5, and IL-13—play an important role.1 2 IL-4 is crucial in activating Janus kinase (JAK), which phosphorylates transcription factor, signal transducer and activator of transcription 6 (STAT6), a key factor for Th2 polarization.3 4 On the other hand, tripartite motif-containing 24 (TRIM24), promotes STAT6 acetylation by catalyzing the ubiquitination of cAMP-responsive element-binding protein (CREB)-binding protein at Lys 119.5 Previous studies have proposed the role of TRIM24 in other diseases, such as head and neck squamous cell carcinoma,6 prostate cancer,7 and breast cancer.8 However, its role in AR has not been explored. In the current issue of Allergy, Asthma & Immunology Research, Yue et al. 9 presented the role of TRIM24 in AR by measuring the expression of TRIM24 in peripheral blood mononuclear cells (PBMCs) and CD4+ T cells from patients with AR and analyzing AR symptoms, IL-4 levels, and proliferation, activation, and polarization of CD4+ T cells in wild-type (WT) and TRIM24-conditional knockout AR mice. Also, the effects of TRIM24 deficiency on STAT6 in CD4+ T cells were analyzed. The expression of TRIM24 in PBMCs and CD4+ T cells from patients with AR was downregulated, while the expression of IL-4 and GATA3 was upregulated in patients with AR. Not only were the instants of nasal rubbing and sneezing higher in TRIM24-knockout AR mice, but also the levels of IL-4, IL-5, and IL-13, Der p 1-specific IgE, number of eosinophils, goblet cell density, and epithelial thickness were elevated in TRIM24-conditional knockout AR mice as well. Although CD4+ T cell proliferation and activation were not different among WT and TRIM24-conditional knockout AR mice, Th2 polarization was greater in TRIM24-knockout CD4+ T cells. Lastly, TRIM24-knockout CD4+ T cells downregulated acetylation of STAT6 and increased STAT6 activity after IL-4 treatment. As aforementioned, the role of TRIM24 in other diseases has been reported. TRIM24 was proposed to be a prognostic biomarker for early detection of local recurrences and survival prognosis in head and neck squamous cell carcinoma6; TRIM24 expression could predict disease recurrence with high accuracy in prostate cancer7; and atypical expression of TRIM24 negatively correlated with survival of patients with breast cancer.8 Likewise, identifying the role of TRIM24 as a biomarker of prognosis or treatment response in AR may be a considerable agenda in future research. For instance, finding a correlation between the symptom severity or long-term prognosis of AR and TRIM24 can help clinicians treat AR patients. In addition, exploration of TRIM24 as a potential therapeutic target for treating AR may also be considered. Regarding the methods for creating the mouse model of AR, an explanation or a reference for administrating 2 different types of antigen, ragweed pollen and Der p1, may better assist the readers’ understanding. In addition, considering the contradiction between the current findings and the previous report,10 in which the expression of TRIM24 protein was elevated in Th2 cells and TRIM24 was essential in Th2-mediated allergy, more studies are recommended to assess the role of TRIM24 in AR. Yue et al.9 delineated the potential role of TRIM24 in suppressing Th2-mediated AR through the acetylation of STAT6. The findings of this study may provide helpful insights to clinicians in understanding the pathophysiological role of TRIM24 and STAT6 in AR.