Unlocking the power of Zc3h12c: Orchestrating Macrophage activation and elevating the innate immune response.

The activation of macrophages, essential for the innate defense against invading pathogens, revolves around Toll-like receptors (TLRs). Nevertheless, a comprehensive understanding of the molecular mechanisms governing TLR signaling in the course of macrophage activation remains to be fully clarified. Although Zc3h12c was originally identified as being enriched in organs associated with macrophages, its precise function remains elusive. In this study, we observed a significant induction of Zc3h12c in macrophages following stimulation with TLR agonists and pathogens. Overexpression of Zc3h12c significantly mitigated the release of TNF-α and IL-6 triggered by lipopolysaccharide (LPS), whereas depletion of Zc3h12c increased the production of the cytokines mentioned above. Notably, the expression of IFN-ß was not influenced by Zc3h12c. Luciferase reporter assays revealed that Zc3h12c could suppress the TNF-α promoter activity. Moreover, Zc3h12c exerted a notable inhibitory effect on JNK, ERK, p38, and NF-κB signaling induced by LPS. In summary, the findings of our study suggest that Zc3h12c functions as a robust suppressor of innate immunity, potentially playing a role in the pathogenesis of infectious diseases.

Correlation between serum immunoglobulin levels and retinal structure in patients with newly diagnosed Vogt­Koyanagi­Harada disease.

Immunoglobulins serve immunomodulatory roles in numerous autoimmune diseases. The aim of the present study was to investigate the correlations between serum Ig levels and retinal structural parameters in patients with newly diagnosed acute Vogt­Koyanagi­Harada (VKH) disease. A total of 138 participants were enrolled and the foveal thickness (FT), serous retinal detachment (SRD), sensory retinal thickness, central FT (CFT), cube volume (V) and cube average thickness (AT) were assessed by optical coherence tomography. The patients were divided, according to the extent of SRD, into a high­detachment group (>500 µm) and a low­detachment group (≤500 µm). Rate­scattering turbidimetry was performed to measure the Ig levels. The high­detachment group comprised 51 (36.96%) patients. The proportion of males was significantly greater in the high­detachment group compared with the low­detachment group (58.82 vs. 40.23%; P<0.05) and best­corrected visual acuity was significantly worse in the high­detachment group compared with the low­detachment group (P<0.001). The IgE levels in the high­detachment group were significantly greater compared with the low­detachment group (P<0.05). FT, SRD, CFT, V and AT were significantly greater in the high­detachment group compared with the low­detachment group (P<0.001). The IgE levels were positively associated with SRD, CFT and AT (P<0.05). Multivariate binary logistic regression analysis demonstrated that male sex (B=2.447; P<0.05) and serum IgE levels (B=0.997, P<0.05) may be independent risk factors for severe SRD. The results of the present study demonstrated that males are more likely to develop severe SRD and that serum IgE levels were associated with the extent of detachment. These data suggested that IgE may be involved in the progression of VKH disease.

Elevated Serum Immunoglobulin E Levels are Associated with the Severity of Newly Diagnosed, Acute Vogt-Koyanagi-Harada Disease.

OBJECTIVE: To investigate the correlation between serum immunoglobulin E (IgE) levels and severity of Vogt-Koyanagi-Harada (VKH) disease. METHODS: The medical records of patients with VKH disease between 2015 and 2020 were reviewed. Serum immunoglobulins (IgA, IgE, IgG, and IgM), tumor necrosis factor α (TNFα) and C-reactive protein (CRP) were measured. Patients were divided into IgE-positive (IgE ≥ 100 IU/mL) and IgE-negative (IgE < 100 IU/mL) groups. The best-corrected visual acuity (BCVA) and macular morphologic characteristics including foveal thickness (FT), serous retinal detachment (SRD), sensory retinal thickness (SRT), central foveal thickness (CFT), cube volume (V), and cube average thickness (AT) were determined in patients in both groups. RESULTS: Of 128 patients included in the study, 35 (27.34%) patients were IgE-positive, BCVA (logMAR) was worse in the IgE-positive group. The mean CRP (P= .012) and TNFα (P≤ 0.001) levels were greater in the IgE-positive group than in the IgE-negative group. Regarding macular morphologic characteristics, FT (P= .010), SDR (P= .004), CFT (P= .008), V (P= .013), and AT (P= .006) were significantly greater in the IgE-positive group than in the IgE-negative group. CONCLUSIONS: Elevated serum IgE levels were associated with more severe macular changes in patients with VKH disease. These findings suggest that IgE may be involved in the progression of VKH disease.