Transcription Factors T-bet/GATA-3/Foxp3 in Peripheral Blood of Patients with Chronic Otitis Media with Effusion
Chronic otitis media with effusion (COME) is a persistent inflammatory condition characterized by the accumulation of fluid in the middle ear cavity, leading to hearing impairment and other related symptoms. This condition, also known as secretory otitis, is a significant cause of hearing loss in both children and adults. The pathogenesis of COME is complex and not entirely understood, but increasing evidence suggests that immune cells and their associated cytokines play a central role in the chronic inflammation observed in COME.
T lymphocytes, particularly helper T cells (Th cells), are the predominant cell types involved in the immune response. Among these, CD4+ T cells are the most abundant. The differentiation of naive T cells into Th1 or Th2 subtypes is mediated by specific cytokines and transcriptional factors. Th1 cells secrete interferon-gamma (IFN-γ) and are regulated by the transcriptional factor T-bet. In contrast, Th2 cells secrete cytokines such as interleukin (IL)-13, IL-5, and IL-4, and their differentiation is regulated by the transcriptional factor GATA3. Regulatory T cells (Treg), which are crucial for maintaining immune tolerance, express CD4, CD25, and Foxp3, and are regulated by the transcriptional factor Foxp3.
The roles of T-bet, GATA-3, and Foxp3 in COME have been investigated through various studies, but the results remain inconclusive. This study aimed to explore the role of these Th1/Th2/Treg-cell-specific transcription factors in the pathogenesis of COME.
The study was conducted at the Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital. Twenty-seven patients (18 males, nine females; mean age: 26.7 ± 16.6 years) with COME and 20 healthy controls (11 males, nine females; mean age: 28.5 ± 18.2 years) were recruited. Subjects older than 14 years were considered adults, while those younger than 14 years were considered children.
Patients with COME primarily reported symptoms such as ear stuffiness, hearing impairment, and secondary tinnitus. A few patients also reported earache. Otoscopic examination revealed retraction or bulging of the tympanic membrane, with partially visible bubbles or fluid levels. Pure tone audiometry showed mild to moderate conductive hearing loss, sometimes accompanied by mixed hearing loss. Tympanometry indicated type “B” or “C” tympanic pressure maps with the absence of acoustic reflex. All patients had a disease duration of more than 3 months. Fourteen patients underwent tympanocentesis or tympanostomy tube insertion for the first time, while 13 patients had two or more episodes. Patients with chronic rhinitis, sinusitis, nasal polyps, nasopharyngeal carcinoma, adenoid hypertrophy, diabetes, tuberculosis, other serious systemic diseases, cancer, blood disorders, and those with a history of steroid therapy in the preceding two weeks were excluded from the study. Healthy controls with no history of allergic disease or adenoid hypertrophy were included.
Blood samples (2 mL) were collected in ethylenediaminetetraacetic acid (EDTA) tubes from all subjects. The samples were processed to extract RNA using TRIzol reagent. The quality of the extracted RNA was checked using agarose gel electrophoresis. Reverse transcription was performed using a reverse transcription kit, and real-time reverse-transcription polymerase chain reaction (RT-PCR) was conducted using SYBR Premix Dimer Eraser. The primers for T-bet, GATA-3, Foxp3, and GAPDH (used as an internal control) were designed and synthesized. The reaction was performed in an ABI PRISM Real-Time PCR System under specific conditions, and the relative expression of target genes was calculated using the 2^-ΔΔCt method.
The study found that the mRNA expression of T-bet in COME patients was significantly higher than that in controls (relative expression: 0.44 ± 0.64 vs. 0.16 ± 0.20, t = -2.17, P = 0.037). Similarly, the mRNA expression of GATA-3 and Foxp3 was also higher in the COME group compared to the control group (relative expression: 0.89 ± 0.99 vs. 0.36 ± 0.36, t = -2.57, P = 0.015, and 1.08 ± 0.79 vs. 0.45 ± 0.48, t = -3.35, P = 0.002, respectively). These findings indicate that Th1, Th2, and Treg cells are increased in patients with COME, with a more significant increase in Th2 and Treg cells. The GATA-3/T-bet expression ratio in the peripheral blood of COME patients was significantly higher than that in normal controls (t = 8.141, P < 0.01), suggesting a higher expression of Th2 cells in the peripheral blood during the progression of COME.
In summary, this study demonstrates that the mRNA expression of T-bet, GATA-3, and Foxp3 is increased in the pathogenesis of COME, indicating that their associated cells, Th1, Th2, and Treg cells, may participate in the progression of COME, particularly Th2 and Treg cells. The imbalance between Th1 and Th2 cells, as indicated by the difference in the GATA-3/T-bet ratio, highlights the potential role of these transcription factors in the pathogenesis of COME.
doi.org/10.1097/CM9.0000000000000292
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