Th1 Cells Alter the Inflammatory Signature of IL-6 by Channeling STAT Transcription Factors to Alu-like Retroelements.
Th1 Cells Alter the Inflammatory Signature of IL-6 by Channeling STAT Transcription Factors to Alu-like Retroelements.
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DOI：
10.4049/jimmunol.2300114
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发表时间：
2023-07-15
期刊：
影响因子：
--
通讯作者：
Jones SA
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文献类型：
--
作者：
Millrine D;Cardus Figueras A;Uceda Fernandez J;Andrews R;Szomolay B;Cossins BC;Rice CM;Li J;Tyrrell VJ;McLeod L;Holmans P;O'Donnell VB;Taylor PR;Turner SJ;Jenkins BJ;Jones GW;Topley N;Williams NM;Jones SA
Th 1细胞在急性炎症期间改变IL-6的转录输出。IL-6和IFN-γ活性联合收割机控制组织对炎症的反应。STAT 1和STAT 3共同调节免疫结果。通过STAT 1和STAT 3转录因子发出信号的细胞因子指导影响组织稳态、抗微生物宿主防御和炎症诱导的组织损伤的决定。为了理解这些活动的协调，我们应用RNA测序、染色质免疫沉淀测序和高通量测序的转座酶可及染色质测定，以鉴定急性消退炎症和引发炎症以驱动纤维化期间小鼠腹膜组织中STAT 1和STAT 3的转录输出。生物信息学重点关注两种情况下免疫调节细胞因子IL-6的转录特征，并研究了促纤维化IFN-γ分泌的CD 4 + T细胞如何改变STAT 1和STAT 3细胞因子线索的解释。在解决炎症时，STAT 1和STAT 3合作驱动影响抗微生物免疫和组织稳态的基质基因表达。IFN-γ分泌性CD 4 + T细胞的引入改变了这种转录程序，并将STAT 1和STAT 3引导到以前潜伏的IFN-γ激活位点基序中。STAT 1和STAT 3结合到这个保守的序列揭示了相互交叉调节和相关的病理生理学基因签名的证据。因此，我们提出效应T细胞通过在炎症中形成STAT 1和STAT 3之间的调节相互作用来重新调节IL-6的转录输出。
Th1 cells alter the transcriptional output of IL-6 during acute inflammation. IL-6 and IFN-γ activities combine to steer tissue responses to inflammation. STAT1 and STAT3 work in partnership to regulate immune outcomes. Cytokines that signal via STAT1 and STAT3 transcription factors instruct decisions affecting tissue homeostasis, antimicrobial host defense, and inflammation-induced tissue injury. To understand the coordination of these activities, we applied RNA sequencing, chromatin immunoprecipitation sequencing, and assay for transposase-accessible chromatin with high-throughput sequencing to identify the transcriptional output of STAT1 and STAT3 in peritoneal tissues from mice during acute resolving inflammation and inflammation primed to drive fibrosis. Bioinformatics focused on the transcriptional signature of the immunomodulatory cytokine IL-6 in both settings and examined how profibrotic IFN-γ–secreting CD4+ T cells altered the interpretation of STAT1 and STAT3 cytokine cues. In resolving inflammation, STAT1 and STAT3 cooperated to drive stromal gene expression affecting antimicrobial immunity and tissue homeostasis. The introduction of IFN-γ–secreting CD4+ T cells altered this transcriptional program and channeled STAT1 and STAT3 to a previously latent IFN-γ activation site motif in Alu-like elements. STAT1 and STAT3 binding to this conserved sequence revealed evidence of reciprocal cross-regulation and gene signatures relevant to pathophysiology. Thus, we propose that effector T cells retune the transcriptional output of IL-6 by shaping a regulatory interplay between STAT1 and STAT3 in inflammation.
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DOI：
10.1126/science.aac7442
发表时间：
2015-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hung T;Pratt GA;Sundararaman B;Townsend MJ;Chaivorapol C;Bhangale T;Graham RR;Ortmann W;Criswell LA;Yeo GW;Behrens TW
通讯作者：
Behrens TW
DOI：
10.1146/annurev-pathol-020712-163930
发表时间：
2013-01-24
期刊：
Annual review of pathology
影响因子：
--
作者：
Duffield JS;Lupher M;Thannickal VJ;Wynn TA
通讯作者：
Wynn TA
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
32.4
作者：
Fielding, Ceri A.;Jones, Gareth W.;McLoughlin, Rachel M.;McLeod, Louise;Hammond, Victoria J.;Uceda, Javier;Williams, Anwen S.;Lambie, Mark;Foster, Thomas L.;Liao, Chia-Te;Rice, Christopher M.;Greenhill, Claire J.;Colmont, Chantal S.;Hams, Emily;Coles, Barbara;Kift-Morgan, Ann;Newton, Zarabeth;Craig, Katherine J.;Williams, John D.;Williams, Geraint T.;Davies, Simon J.;Humphreys, Ian R.;O'Donnell, Valerie B.;Taylor, Philip R.;Jenkins, Brendan J.;Topley, Nicholas;Jones, Simon A.
通讯作者：
Jones, Simon A.
DOI：
10.4161/jkst.20045
发表时间：
2012-04-01
期刊：
JAK-STAT
影响因子：
--
作者：
Avalle L;Pensa S;Regis G;Novelli F;Poli V
通讯作者：
Poli V