Several studies have tried to establish mice models of atopic dermatitis (AD) through the allergen of Dermatophagoides farinae (Df). However, there are no typical skin lesions after epicutaneous application of an extract of Df (DfE) on BALB/c mice. Dinitrofluorobenzene (DNFB) is a common hapten that brings about contact dermatitis. Skin dysfunction induced by DNFB may be a way to enhance the effects of DfE on mice skin. Thus, we hypothesized that alternate epicutaneous application of DNFB and DfE could induce AD-like skin lesions on BALB/c mice. To test this hypothesis, we alternately applied the DNFB and DfE to the back skin of BALB/c mice for 8 weeks. Changes in mice skin lesions and the frequency of scratching behavior were recorded. The variation of Th1-related cytokines (interferon-γ [IFN-γ] and interleukin two [IL-2]) and Th2-related cytokines (IL-4 and IL-13) was detected in serum and lesional skin. Eventually, the BALB/c mice developed severe erythema, erosion, scarring, and excoriation on the entire back, showing a high frequency of scratching behavior. In addition, Th2 cells' dominant cytokines appeared in both serum and lesional skin. Those results indicate that alternating epicutaneous exposure to DNFB and DfE can produce AD-like models with typical clinical features and Th2-type immune responses in BALB/c mice. This model could be valuable for studying the pathogenesis of AD and developing novel therapeutic agents for it.
Atopic dermatitis (AD) is a common inflammatory skin disease, but current treatments for AD are mostly limited to the alleviation of symptoms and inhibition of inflammation. Allergen‐specific immunotherapy (ASIT) is the only curative approach for allergic diseases and could be a promising way to cure AD. Although ASIT has been gradually applied to patients with AD, there are still few studies on its efficacy evaluation and mechanisms. Based on our previous established AD mouse model by dinitrofluorobenzene and an extract of Dermatophagoides farina, we performed ASIT on this AD model through subcutaneous injection of Dermatophagoides farina extracts to evaluate the efficacy of ASIT and study its underlying mechanisms. Our results showed that ASIT could not only alleviate skin lesions and scratching behaviors of AD mice but also inhibit their Th2‐type immune responses. Furthermore, ASIT could increase the infiltration of monocyte‐derived dendritic cells in skin lesions but attenuated their maturation and production of interleukin 1α and interleukin 12/23 p40. As immature and semi‐mature dendritic cells preferentially induce tolerance, accumulation but inhibition of maturation of monocyte‐derived dendritic cells after ASIT may indicate a novel mechanism of ASIT and a potential therapeutic target for AD.
Objective The purpose of this study was to explore the effect of CRABP2 and FABP5, and their ratio on prognosis in esophageal squamous cell carcinoma. Methods The expression data of CRABP2 in esophageal cancer in TCGA and GEO were collected by the public database GEPIA. The expression levels of CRABP2 and FABP5 were examined using immunohistochemistry. The relationship between the two proteins and related clinicopathological parameters were analyzed by χ 2 test. Survival analysis was used to investigate the effect of CRABP2 and FABP5, and their ratio on prognosis. Results Compared with normal esophageal mucosal epithelium, there was lower CRABP2 gene mRNA in the esophageal cancer tissue, and the difference was statistically significant (p < 0.01). For the expression level, no significant difference was observed in patients with stages I–IV in esophageal cancer. Immunohistochemistry showed that CRABP2 and FABP5 were both highly expressed in normal esophageal squamous epithelial cells at 100 and 94.1%, while lower in ESCC (75.6 and 58.7%). There was a significant difference in the expression between cancer and adjacent tissues (p < 0.001). No inherent relationship was manifested between the CRABP2 expression and the clinical parameters of the ESCC. The expression of FABP5 was related to lymph node metastasis (p = 0.032), the depth of invasion (p = 0.041), and the AJCC stage (p = 0.013). The ratio of CRABP2 and FABP5 was related to ethnicity (p = 0.001), nerve invasion (p = 0.031), and postoperative treatment (p = 0.038). CRABP2 is positively associated with FABP5 (r = 0.156, p = 0.041) and the ratio (r = 0.334, p = 0.000), while there was a negative correlation between FABP5 and the ratio (r = −0.269, p = 0.000). Patients with CRABP2-positive expression had a significantly longer overall survival than patients with CRABP2-negative expression (p = 0.025). Conclusion CRABP2 as a suppressor factor is expected to be a potential prognosis marker for esophageal squamous cell carcinoma.
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