輔助性T細胞高維分析揭示穩定效應因子狀態的多樣性及譜系間關係
作者:
小柯機器人發布時間:2020/8/1 23:45:40
瑞士蘇黎世聯邦理工學院Manfred Kopf和Luigi Tortola研究團隊在研究中取得進展。他們通過對輔助性(Th)T細胞進行高維分析揭示了穩定效應因子狀態的廣泛多樣性及譜系間的關係。相關論文於2020年7月30日在線發表在《免疫》雜誌上。
研究人員利用細胞計數法分析了體外和動物疾病模型中產生Th細胞反應的多樣性,揭示了具有不同細胞因子印記效應因子狀態的巨大異質性。在Th1和Th2細胞極化條件下初次抗原相遇期間建立的細胞因子反應多樣性在二次抗原刺激下才能維持,而這與新炎症環境無關,這突出了許多已鑑定的細胞狀態為穩定Th細胞的亞系。研究人員還發現,在受到刺激後Th17細胞趨於上調與Th2細胞相關的細胞因子,這表明Th17與Th2細胞之間的發展聯繫比以前預期的更緊密。
據悉,CD4+Th細胞是免疫系統的基石。按照標誌性細胞因子和轉錄因子的表達情況已經定義了幾個Th亞群。人們認為Th細胞的異質性和功能性要比最初認為的要高得多,但是由於技術上的限制,無法充分表徵其多樣性。
附:英文原文
Title: High-Dimensional T Helper Cell Profiling Reveals a Broad Diversity of Stably Committed Effector States and Uncovers Interlineage Relationships
Author: Luigi Tortola, Andrea Jacobs, Lea Pohlmeier, Franz-Josef Obermair, Franziska Ampenberger, Bernd Bodenmiller, Manfred Kopf
Issue&Volume: 2020-07-30
Abstract: CD4+ T helper (Th) cells are fundamental players in immunity. Based on the expressionof signature cytokines and transcription factors, several Th subsets have been defined.Th cells are thought to be far more heterogeneous and multifunctional than originallybelieved, but characterization of the full diversity has been hindered by technicallimitations. Here, we employ mass cytometry to analyze the diversity of Th cell responsesgenerated in vitro and in animal disease models, revealing a vast heterogeneity of effector states withdistinct cytokine footprints. The diversities of cytokine responses established duringprimary antigen encounters in Th1- and Th2-cell-polarizing conditions are largelymaintained after secondary challenge, regardless of the new inflammatory environment,highlighting many of the identified states as stable Th cell sublineages. We alsofind that Th17 cells tend to upregulate Th2-cell-associated cytokines upon challenge,indicating a closer developmental connection between Th17 and Th2 cells than previouslyanticipated.
DOI: 10.1016/j.immuni.2020.07.001
Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30281-8