Interferon regulatory factor 8 integrates T-cell receptor and cytokine-signaling pathways and drives effector differentiation of CD8 T cells
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TLDR
Collectively, this work shows that IRF8 integrates the TCR/costimulation and γc-cytokine–signaling pathways and mediates the transition of naive CD8 T cells to effector cells, thus identifying IRF 8 as one of the molecular regulators ofCD8 T-cell differentiation.Abstract:
We recently demonstrated that differentiation of cytotoxic T cells requires cooperation between T-cell receptor (TCR)/costimulation and γc-cytokines. Here we demonstrate that the transcription factor IFN regulatory factor 8 (IRF8) is expressed in CD8 T cells by the combination of these two signals. More importantly, depletion of IRF8 in these cells abrogated the differentiation of naive CD8 T cells into effector cells in an experimental graft-vs.-host disease mouse model. We also show that IRF8 seems to not operate upstream of other critical factors such as T-bet and eomesodermin, which have been implicated in effector maturation. Collectively, our work shows that IRF8 integrates the TCR/costimulation and γc-cytokine–signaling pathways and mediates the transition of naive CD8 T cells to effector cells, thus identifying IRF8 as one of the molecular regulators of CD8 T-cell differentiation.read more
Citations
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Manganese is critical for antitumor immune responses via cGAS-STING and improves the efficacy of clinical immunotherapy
Mengze Lv,Mengze Lv,Meixia Chen,Rui Zhang,Wen Zhang,Wen Zhang,Chenguang Wang,Yan Zhang,Xiaoming Wei,Yukun Guan,Yukun Guan,Jiejie Liu,Kaichao Feng,Miao Jing,Xurui Wang,Yun-Cai Liu,Qian Mei,Weidong Han,Zhengfan Jiang +18 more
TL;DR: A completed phase 1 clinical trial with the combined regimen of Mn2+ and anti-PD-1 antibody showed promising efficacy, exhibiting type I IFN induction, manageable safety and revived responses to immunotherapy in most patients with advanced metastatic solid tumors.
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Distinct Epigenetic Signatures Delineate Transcriptional Programs during Virus-Specific CD8+ T Cell Differentiation
Brendan E. Russ,Moshe Olshanksy,Heather S. Smallwood,Jasmine Li,Alice E. Denton,Julia E. Prier,Angus T. Stock,Hayley A Croom,Jolie G. Cullen,Michelle L.T. Nguyen,Stephanie Rowe,Matthew R. Olson,David B. Finkelstein,Anne Kelso,Paul G. Thomas,Terry P. Speed,Sudha Rao,Stephen J. Turner +17 more
TL;DR: Assessment of histone H3 methylation dynamics within naive, effector, and memory virus-specific T cells isolated directly ex vivo after influenza A virus infection shows coordinate transcriptional regulation of CTL genes with related functions is achieved via distinct epigenetic mechanisms.
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An osteopontin/CD44 immune checkpoint controls CD8+ T cell activation and tumor immune evasion
John D. Klement,Amy V. Paschall,Amy V. Paschall,Priscilla S. Redd,Priscilla S. Redd,Mohammed L. Ibrahim,Chunwan Lu,Chunwan Lu,Dafeng Yang,Dafeng Yang,Esteban Celis,Scott I. Abrams,Keiko Ozato,Kebin Liu,Kebin Liu +14 more
TL;DR: It is reported here that interferon regulatory factor 8 (IRF8) deficiency led to impairment of cytotoxic T lymphocyte (CTL) activation and allograft tumor tolerance and that OPN acts as an immune checkpoint to suppress T cell activation and confer host tumor immune tolerance.
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The transcription factor IRF8 activates integrin-mediated TGF-β signaling and promotes neuroinflammation.
Yuko Yoshida,Ryusuke Yoshimi,Hiroaki Yoshii,Daniel Kim,Anup Dey,Huabao Xiong,Jeeva Munasinghe,Itaru Yazawa,Michael J. O'Donovan,Olga A. Maximova,Suveena Sharma,Jinfang Zhu,Hongsheng Wang,Herbert C. Morse,Keiko Ozato +14 more
TL;DR: It is found that Irf8(-/-) mice are resistant to EAE, and mechanistic bases by which IRF8 contributes to the pathogenesis of MS are provided.
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Cholesterol negatively regulates IL-9–producing CD8+ T cell differentiation and antitumor activity
Xingzhe Ma,Enguang Bi,Chunjian Huang,Yong Lu,Gang Xue,Xing Guo,Aibo Wang,Maojie Yang,Jianfei Qian,Chen Dong,Qing Yi +10 more
TL;DR: Cholesterol is identified as a critical regulator of Tc9 cell differentiation and function and is associated with stronger antitumor responses than classical Tc1 cells.
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