2015-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/644273摘要：異位性皮膚炎是常見的慢性發炎性皮膚疾病。其致病機轉複雜，包括基因傾向、免疫異常、環境過敏原暴露和引發因子的交互作用。許多細菌存在皮膚上。異位性皮膚炎和皮膚微生物群之間的交互作用，以及金黃色葡萄球菌和常見共生菌之間競爭性平衡和異位性皮膚炎之間的交互作用已被一再強調。最近，細菌的代謝產物，短鏈脂肪酸被證實可以調控發炎和免疫反應，並提高調節性T細胞的生成。而且皮膚上的常見共生菌曾被報告可以產生這些短鏈脂肪酸。我們假設短鏈脂肪酸可以經由抑制金黃色葡萄球菌及提高調節性T細胞的作用，而調控異位性皮膚炎。我們將使用異位性皮膚炎小鼠模型，並分析病人病灶和血液的檢體，來檢驗此假說。本研究計畫有下列特定目標：一、 利用異位性皮膚炎小鼠模型，來研究短鏈脂肪酸對致敏和作用階段所引導之第一/第二/第十七型T細胞反應的影響。二、 利用異位性皮膚炎小鼠模型，來研究短鏈脂肪酸對致敏和作用階段所引導之調節性T細胞的影響。三、 研究異位性皮膚炎致病機轉中，金黃色葡萄球菌、活化之第二型細胞素生成細胞和慢性發炎之間的分子關連。四、 偵測異位性皮膚炎病人病灶之金黃色葡萄球菌、共生菌、短鏈脂肪酸和細胞素的數量和性狀，以及短鏈脂肪酸對調節性T細胞的影響。此研究計畫所獲得之結論，預期將釐清共生菌、金黃色葡萄球菌、短鏈脂肪酸在異位性皮膚炎致病機轉中的角色，並且了解他們和類鐸受體訊號傳遞途徑以及調節性T細胞之間的交互作用。這些資料可以大幅提高我們對異位性皮膚炎致病機轉的了解，幫助我們研發此病的新型治療方法和藥物。<br> Abstract: Atopic dermatitis (AD) is a common chronic inflammatory skin disease. The pathogenesis of AD involves a complex interplay of genetic predisposition, immune dysfunction, environmental allergen exposure and trigger factors.A variety of microbes reside on skin. The interaction of AD and skin microbiome as well as competitive balance between S. aureus and common commensal have been emphasized. Recently, the microbial metabolites, short chain fatty acids (SCFAs) have been demonstrated to shape immunity, regulate inflammation and promote peripheral regulatory T cell generation. Moreover, production of SCFAs by skin common commensal has been reported.We hypothesize that SCFAs modulate AD through inhibition of S. aureus and promotion of regulatory T cells. We will use murine AD models and analyze human blood and skin samples to examine this hypothesis. The following four specific aims will be achieved:Specific aim 1: To investigate the effects of short chain fatty acids (SCFAs) on the Th1/Th2/Th17 responses in murine atopic dermatitis models in BALB/c and B6 mice, including sensitization and effector phases.Specific aim 2: To elucidate the effects of SCFAs on Treg cells in sensitization and effector phases.Specific aim 3: To study a molecular link between S. aureus, activated Th2 cytokine-producing cells, and chronic inflammation in the pathogenesis of AD.Specific aim 4: To measure S. aureus, commensal bacteria, SCFAs and cytokines in AD skins and to measure the effects of SCFAs on Treg cells.The results from this subproject are expected to validate the contributions of common commensal, S. aureus, and SCFAs to the pathogenesis of AD as well as their interactions with TLRs signaling pathway and induction of Treg cells and cytokines. The information obtained from this subproject is expected to greatly improve our understanding of the pathogenesis of AD and help develop novel treatments.異位性皮膚炎微生物群短鏈脂肪酸類鐸受體調節性T細胞atopic dermatitismicrobiomeshort chain fatty acidsToll-like receptorregulatory T cell