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上海士鋒生物關(guān)于白細胞介素-23調(diào)節(jié)免疫記憶Th17細胞
點擊次數(shù):1656 發(fā)布時間:2013-5-3
白細胞介素-23調(diào)節(jié)免疫記憶Th17細胞
白細胞介素-23(IL-23)對于免疫記憶Th17細胞的分化具有重要作用,但是IL-23在記憶Th17細胞的具體作用仍然不清楚。
本次研究中,研究人員通過建立實驗用的免疫性腦脊髓炎模型,發(fā)現(xiàn),當二次感染腦膜炎時,記憶Th17細胞會快速增值并大量的轉(zhuǎn)移到中樞神經(jīng)系統(tǒng)中。免疫記憶Th17細胞的前體是IL-17 +和RORγT ,記憶Th17細胞表型的穩(wěn)定性依賴于一次免疫應(yīng)答所花費的時間。IL-23受體的阻斷不會直接影響Th17前體IL-17 的產(chǎn)生,但是卻抑制Th17 細胞的增殖和Th1細胞特異性轉(zhuǎn)錄抑制因子T-bet的共表達。此外,如果無法結(jié)合IL-23,Th17 細胞中很多和細胞周期有關(guān)的基因就會被下調(diào),從而被抑制表達。所以,此項研究表明了在一次免疫中的白細胞介素-23的功能和記憶Th17細胞通過增殖調(diào)節(jié)免疫的路徑。
Autoimmune Memory T Helper 17 Cell Function and Expansion Are Dependent on Interleukin-23
Christopher J. Haines,Yi Chen,Wendy M. Blumenschein,Renu Jain,Charlie Chang,Barbara Joyce-Shaikh,Katherine Porth,Katia Boniface,Jeanine Mattson,Beth Basham,Stephen M. Anderton,Terrill K. McClanahan,Svetlana Sadekova,Daniel J. Cua,Mandy J. McGeachy
Interleukin-23 (IL-23) is essential for the differentiation of pathogenic effector T helper 17 (Th17) cells, but its role in memory Th17 cell responses is unclear. Using the experimental autoimmune encephalomyelitis (EAE) model, we report that memory Th17 cells rapidly expanded in response to rechallenge and migrated to the CNS in high numbers, resulting in earlier onset and increased severity of clinical disease. Memory Th17 cells were generated from IL-17+ and RORγt+ precursors, and the stability of the Th17 cell phenotype depended on the amount of time allowed for the primary response.