Neonatal Immune State Is Influenced by Maternal Allergic Rhinitis and Associated With Regulatory T cells

Lu Tan,Jing Ou,Zezhang Tao,Yonggang Kong,Yuxuan Zhang 대한천식알레르기학회 2017 Allergy, Asthma & Immunology Research Vol.9 No.2

Purpose: Maternal influences contribute to the origin of allergic diseases, but the mechanisms are not clear. The current literature prompted the role of epigenetics in the development of allergic diseases. We sought to investigate the roles of regulatory T (Treg) cells and Forkhead box p3 (Foxp3) DNA methylation in the process of maternal transmission of allergic rhinitis (AR) susceptibility. Methods: BALB/c female mice (AR mother) were sensitized by intraperitoneal injection of Dermatophagoides pteronyssinus (Der p) 1 on day 1 and 7. Then they mated with normal male mice on day 8. From day 21 to 28, the female mice were intranasal challenged with Der p 1 continuously. The normal controls were given with normal saline in the same way. On postnatal day 3, Female mice and their offspring were sacrificed to detect their histopathology in nasal mucosae, cytokines in sera of mother and spleen homogenates of offspring, Treg cells count, Foxp3 mRNA expressions, and Foxp3 DNA methylation levels in spleens. Results: Compared with the normal controls, neonatal offspring of Der p 1-stimulated female mice (AR offspring) showed the elevation of interleukin (IL)-4 (P<0.01) and IL-17 (P<0.01), the submission of IL-10 (P<0.01) in spleen homogenates. Further, Treg cells count in AR offspring decreased remarkably compared with the normal offspring (P<0.01). Though the difference of Foxp3 DNA methylation level between AR offspring and normal control offspring was not obvious, correlation analysis demonstrated that there was significantly positive correlation between Foxp3 DNA methylation level of mother and that of offspring (r=0.803, P<0.01). Conclusions: Under the influence of Maternal AR, their neonatal offspring develop into T-helper type 2 (Th2) dominant immune state, which is closely associated with the recession of Treg cells. Foxp3 DNA methylation may be a mechanism responsible for that maternal effect but still need more studies to ensure.

Activation of Dopamine D2 Receptor Alleviates Neuroinflammation in a Mouse Model of Allergic Rhinitis With Olfactory Dysfunction

Liu Peiqiang,Qin Danxue,Lv Hao,Fan Wenjun,Zhou Fangwei,Gao Ziang,Tao Zezhang,Xu Yu 대한천식알레르기학회 2021 Allergy, Asthma & Immunology Research Vol.13 No.6

Purpose: Allergic rhinitis (AR) is a common otolaryngology disease and one of the clinical causes of olfactory dysfunction (OD). The olfactory bulb serves as a transfer station for olfactory information transmission, and alleviating its neuroinflammation may be expected to improve AR-induced OD. Recent studies have suggested that the dopamine D2 receptor acts as a key target in regulating immune functions and neuroinflammatory reaction. However, the effect of dopamine D2 receptor on AR-induced neuroinflammation is still unknown. Methods: An AR mouse model with OD induced by ovalbumin were constructed. The buried food pellet test was to evaluate the olfactory function of the mice. Immunofluorescence staining, hematoxylin and eosin staining, enzyme-linked immunosorbent assay and western blotting were also used to investigate the molecular mechanisms underlying the antiinflammatory effects of the dopamine D2 receptor in AR-induced OD. Results: We found that AR-induced OD has a relationship with inflammatory responses in the olfactory bulb. Nasal administration of quinpirole (Quin, a dopamine D2 receptor agonist, 3 mg/kg) improved olfactory function in mice, inhibited the expression of toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signalings and the levels of tumor necrosis factor-α, interleukin (IL)-1β and IL-6 in the olfactory bulb. In vitro, Quin (20 μmol/L) inhibited the release of TLR4/NF-κB signalings-dependent inflammatory cytokines in cultured microglia. Conclusions: Activation of the dopamine D2 receptor inhibits the release of inflammatory cytokines through TLR4/NF-κB signaling in the olfactory bulb microglia, and protects olfactory function.

Ginkgolic Acid Suppresses Nasopharyngeal Carcinoma Growth by Inducing Apoptosis and Inhibiting AKT/NF-κB Signaling

Yu Xiao,Fen Li,Anyuan Zheng,Qibing Chen,Fuhai Chen,Xiang Cheng,Zezhang Tao 한국식품영양과학회 2021 Journal of medicinal food Vol.24 No.8

Even though nasopharyngeal carcinoma (NPC) is not common worldwide, it is a major public health burden in endemic areas. Distant metastasis often leads to a poor prognosis for NPC; therefore, new and effective anticancer strategies are needed. Ginkgolic acid (GA) is small-molecule compound existing in Ginkgo biloba that has various biologically relevant activities, including antitumor properties; however, its effects and mechanism of action in NPC are unknown. The effects of GA on NPC and such underlying mechanisms were investigated using 5–8F and CNE2 cells and NP69 human immortalized nasopharyngeal epithelial cells in this study. Moreover, the xenograft models were built to examine GA's effection in vivo. GA treatment decreased the survival and invasive capacity of 5–8F and CNE2 and induced their apoptosis, which varied with dose; this was accompanied by downregulation of B cell lymphoma (Bcl)2, upregulation of Bcl2-associated X protein, and activation of poly-ADP ribose polymerase, and caspase-9/-3. G0/G1 phase arrest was induced by GA in NPCs. It also reduced the expression of cyclin-dependent kinase 6 and its regulators cyclin D2 and cyclin D3. GA inhibited the activation of protein kinase B/nuclear factor signaling; this effect was potentiated with GA and 5-fluorouracil (5-FU), which also enhanced 5-FU-induced apoptosis. In summary, GA may be effective as an adjuvant to conventional chemotherapy drugs in preventing the progression of NPC.

TET2 Regulates 5-Hydroxymethylcytosine Signature and CD4+ T-Cell Balance in Allergic Rhinitis

Tan Lu,Fu Lisheng,Zheng Li,Fan Wenjun,Tan Hanyu,Tao Zezhang,Xu Yu 대한천식알레르기학회 2022 Allergy, Asthma & Immunology Research Vol.14 No.2

Purpose: Previous studies have shown the role of ten-eleven translocation 2 (TET2) in CD4+ T cells. However, its function in CD4+ T cells under allergic inflammation is unclear. We aimed to investigate the epigenomic distribution of DNA 5-hydroxymethylcytosine (5hmC) and the role of TET2 in CD4+ T cells of allergic rhinitis (AR). Methods: The hMeDIP-seq was performed to identify sequences with 5hmC deposition in CD4+ T cells of AR patients. Tet2-deficient or wild type mice were stimulated with ovalbumin (OVA) to develop an AR mouse model. The histopathology in nasal mucosae, Th1/Th2/Treg/Th17 cell percentage, concentrations of Th-related cytokines, expression of Tet and differential hydroxymethylated genes (DhMG), and the global deposition of 5hmC in sorted CD4+ T cells were detected. Results: Epigenome-wide 5hmC landscape and DhMG in the CD4+ T cells of AR patients were identified. Tet2 depletion did not led to spontaneous inflammation. However, under the stimulation of allergen, OVA, loss of Tet2 resulted in the exacerbation of allergic inflammation, which was characterized by severer allergic symptoms, more inflammatory cells infiltrating the nasal lamina propria, sharper imbalances between Th1/Th2 and Treg/Th17 cells, and excessive secretion of OVA-specific IgE and Th2-related cytokines. Moreover, altered mRNA production of several DhMG and sharp decrease in 5hmC deposition were also observed in Tet2-deficient OVA-exposed mice. Conclusions: TET2 may regulate DNA 5hmC, DhMG expressions, and CD4+ T cell balance in AR.

Chinese Society of Allergy Guidelines for Diagnosis and Treatment of Allergic Rhinitis

Lei Cheng,Jianjun Chen,Qingling Fu,Shaoheng He,Huabin Li,Zheng Liu,Guolin Tan,Zezhang Tao,Dehui Wang,Weiping Wen,Rui Xu,Yu Xu,Qintai Yang,Chonghua Zhang,Gehua Zhang,Ruxin Zhang,Yuan Zhang,Bing Zhou,Do 대한천식알레르기학회 2018 Allergy, Asthma & Immunology Research Vol.10 No.4

Allergic rhinitis (AR) is a global health problem that causes major illnesses and disabilities worldwide. Epidemiologic studies have demonstrated that the prevalence of AR has increased progressively over the last few decades in more developed countries and currently affects up to 40% of the population worldwide. Likewise, a rising trend of AR has also been observed over the last 2-3 decades in developing countries including China, with the prevalence of AR varying widely in these countries. A survey of self-reported AR over a 6-year period in the general Chinese adult population reported that the standardized prevalence of adult AR increased from 11.1% in 2005 to 17.6% in 2011. An increasing number of original articles and imporclinical trials on the epidemiology, pathophysiologic mechanisms, diagnosis, management and comorbidities of AR in Chinese subjects have been published in international peer-reviewed journals over the past 2 decades, and substantially added to our understanding of this disease as a global problem. Although guidelines for the diagnosis and treatment of AR in Chinese subjects have also been published, they have not been translated into English and therefore not generally accessible for reference to non-Chinese speaking international medical communities. Moreover, methods for the diagnosis and treatment of AR in China have not been standardized entirely and some patients are still treated according to regional preferences. Thus, the present guidelines have been developed by the Chinese Society of Allergy to be accessible to both national and international medical communities involved in the management of AR patients. These guidelines have been prepared in line with existing international guidelines to provide evidence-based recommendations for the diagnosis and management of AR in China.