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| 1 | 放疗或化疗诱导淋巴细胞减少联合免疫重建和瘤苗免疫显示文摘目的利用淋巴细胞减少期T细胞发生增殖活化的原理,以全身照射或环磷酰胺引起淋巴细胞减少,联合免疫重建及肿瘤疫苗免疫,以增强机体的肿瘤特异性免疫反应。方法分别以放疗或化疗(环磷酰胺)引起小鼠淋巴细胞减少,然后输入同系小鼠的未致敏脾细胞,建立免疫重建的淋巴细胞减少小鼠模型(RLM)。用黑色素瘤细胞F10对前者行免疫肿瘤攻击实验,并行T细胞亚群清除试验。而化疗RLM免疫模型的抗肿瘤免疫反应效果通过过继免疫治疗检测。免疫用瘤苗为GMCSF修饰的黑色素瘤细胞D6G6。免疫后9~10d,采集肿瘤疫苗接种部位的引流淋巴结,制备效应T细胞,然后过继回输给荷瘤3d(D5)的小鼠。2周后处死小鼠,计数肺转移灶数目。结果63.2%的放疗RLM免疫组小鼠可对肿瘤攻击产生抵抗,显著高于正常免疫组(16.7%,P<0.0001)。CD8+T细胞是介导抗肿瘤保护性免疫的主要效应细胞。延长免疫重建和瘤苗接种之间的间隔可削弱保护性抗肿瘤免疫。化疗RLM免疫组效应T细胞的在体抗肿瘤活性显著强于正常免疫组。结论在放、化疗引起的淋巴细胞减少期进行瘤苗免疫,有助于打破机体对肿瘤的免疫耐受,增强抗肿瘤免疫反应。 | 马军 王一理 HU Hong-ming Bernard A.Fox 司履生 | 2005 | 中华肿瘤杂志2005，27，8： | 5 |
| 2 | Macrophages are the primary effector cells in IL-7-induced arthritis显示文摘Synovial macrophages are crucial in the development of joint inflammation and bone damage;however, the pathways that controlmacrophage remodeling in inflammatory M1 cells or bone-eroding osteoclasts are not fully understood. We determined thatelevated IL-7R/CD127 expression is the hallmark of rheumatoid arthritis (RA) M1 macrophages and that these cells are highlyresponsive to interleukin-7 (IL-7)-driven osteoclastogenesis. We established that lipopolysaccharide (LPS), interferon-γ (IFNγ), andtumor necrosis factor-α (TNFα), the classic M1 macrophage mediators, enhance IL-7R expression in RA and murine macrophages.The local expression of IL-7 provokes arthritis, predominantly through escalating the number of F480^(+)iNOS^(+) cells rather than CD3^(+)T cells. Ectopic LPS injection stabilizes IL-7-induced arthritis by increasing myeloid IL-7R expression, in part via IFNγ induction.Hence, in RAG−/− mice, IL-7-mediated arthritis is suppressed because of the reduction in myeloid IL-7R expression due to the lackof IFNγ. Moreover, the amelioration of IL-7-induced arthritis by anti-TNF therapy is due to a decrease in the number of cells in theunique F480^(+)iNOS^(+)IL-7R^(+)CCL5^(+) subset, with no impact on the F480^(+)Arginase^(+) cell or CD3^(+) T cell frequency. Consistent with thepreclinical findings, the findings of a phase 4 study performed with RA patients following 6 months of anti-TNF therapy revealedthat IL-7R expression was reduced without affecting the levels of IL-7. This study shifts the paradigm by discovering that IL-7-induced arthritis is dependent on F480^(+)iNOS^(+)IL-7R^(+)CCL5^(+) cell function, which activates TH-1 cells to amplify myeloid IL-7Rexpression and disease severity. | Seung-jae Kim Huan J.Chang Michael VVolin Sadiq Umar Katrien Van Raemdonck Aimee Chevalier Karol Palasiewicz John W.Christman Suncica Volkov Shiva Arami Mehrdad Maz Anjali Mehta Ryan K.Zomorrodi David A.Fox Nadera Sweiss Shiva Shahrara | 2020 | Cellular & Molecular Immunology2020，17，7： | 4 |
| 3 | IRAK4 inhibition: a promising strategy for treating RA joint inflammation and bone erosion显示文摘Flares of joint inflammation and resistance to currently available biologic therapeutics in rheumatoid arthritis(RA)patients could reflect activation of innate immune mechanisms.Herein,we show that a TLR7 GU-rich endogenous ligand,miR-Let7b,potentiates synovitis by amplifying RA monocyte and fibroblast(FLS)trafficking.miR-Let7b ligation to TLR7 in macrophages(MΦs)and FLSs expanded the synovial inflammatory response.Moreover,secretion of M1 monokines triggered by miR-Let7b enhanced Th1/Th17 cell differentiation.We showed that IRAK4 inhibitor(i)therapy attenuated RA disease activity by blocking TLR7-induced M1 MΦor FLS activation,as well as monokine-modulated Th1/Th17 cell polarization.IRAK4i therapy also disrupted RA osteoclastogenesis,which was amplified by miR-Let7b ligation to joint myeloid TLR7.Hence,the effectiveness of IRAK4i was compared with that of a TNF inhibitor(i)or anti-IL-6R treatment in collagen-induced arthritis(CIA)and miR-Let7b-mediated arthritis.We found that TNF or IL-6R blocking therapies mitigated CIA by reducing the infiltration of joint F480+iNOS+MΦs,the expression of certain monokines,and Th1 cell differentiation.Unexpectedly,these biologic therapies were unable to alleviate miR-Let7b-induced arthritis.The superior efficacy of IRAK4i over anti-TNF or anti-IL-6R therapy in miR-Let7b-induced arthritis or CIA was due to the ability of IRAK4i therapy to restrain the migration of joint F480+iNOS+MΦs,vimentin+fibroblasts,and CD3+T cells,in addition to negating the expression of a wide range of monokines,including IL-12,MIP2,and IRF5 and Th1/Th17 lymphokines.In conclusion,IRAK4i therapy may provide a promising strategy for RA therapy by disconnecting critical links between inflammatory joint cells. | Sadiq Umar Karol Palasiewicz Katrien Van Raemdonck Michael V.Volin Bianca Romay MAsif Amin Ryan K.Zomorrodi Shiva Arami Mark Gonzalez Vikram Rao Brian Zanotti David A.Fox Nadera Sweiss Shiva Shahrara | 2021 | Cellular & Molecular Immunology2021，18，9： | 1 |
| 4 | Consumer demand for and attitudes toward alternative beef labeling strategies in France, Germany, and the UK显示文摘 | JuttaRoosen Jayson L.Lusk John A.Fox | 2003 | Agribusiness2003，，1： | 1 |
| 5 | The Relations Between Temperament and Empathy in 2-YearOlds显示文摘 | Shari K.Young Nathan A.Fox Carolyn Zahn-Waxler | | 0，，05： | 1 |
| 6 | The role of CD6 in autoimmune diseases显示文摘In a recent publication in the Cellular and Molecular Immunology,Consuega-Fernandez and colleagues present new data from patients with psoriasis,linking the CD6 lymphocyte surface structure to the pathogenesis of this disease.1 In this commentary,I will discuss these new findings in the context of accumulating evidence for important roles of CD6 in a variety of autoimmune disorders.Although CD6 was one of the earliest“CD antigens”to be described,it is only recently that attention has refocused on the potential for CD6 as a treatment target in immune-mediated diseases. | David A.Fox | 2018 | Cellular & Molecular Immunology2018，15，11： | 1 |
| 7 | Is there a rationale for output-based rebating of environmental levies显示文摘 | Bernard A C.Fischer A.Fox | | 0，，02： | 1 |
| 8 | Extracellular sulfatase-2 is overexpressed in rheumatoid arthritis and mediates the TNF-α-induced inflammatory activation of synovial fibroblasts显示文摘Extracellular sulfatase-2(Sulf-2)influences receptor-ligand binding and subsequent signaling by chemokines and growth factors,yet Sulf-2 remains unexplored in inflammatory cytokine signaling in the context of rheumatoid arthritis(RA).In the present study,we characterized Sulf-2 expression in RA and investigated its potential role in TNF-α-induced synovial inflammation using primary human RA synovial fibroblasts(RASFs).Sulf-2 expression was significantly higher in serum and synovial tissues from patients with RA and in synovium and serum from hTNFtg mice.RNA sequencing analysis of TNF-α-stimulated RASFs showed that Sulf-2 siRNA modulated~2500 genes compared to scrambled siRNA.Ingenuity Pathway Analysis of RNA sequencing data identified Sulf-2 as a primary target in fibroblasts and macrophages in RA.Western blot,ELISA,and qRT‒PCR analyses confirmed that Sulf-2 knockdown reduced the TNF-α-induced expression of ICAM1,VCAM1,CAD11,PDPN,CCL5,CX3CL1,CXCL10,and CXCL11.Signaling studies identified the protein kinase C-delta(PKCδ)and c-Jun N-terminal kinase(JNK)pathways as key in the TNF-α-mediated induction of proteins related to cellular adhesion and invasion.Knockdown of Sulf-2 abrogated TNF-α-induced RASF proliferation.Sulf-2 knockdown with siRNA and inhibition by OKN-007 suppressed the TNF-α-induced phosphorylation of PKCδand JNK,thereby suppressing the nuclear translocation and DNA binding activity of the transcription factors AP-1 and NF-κBp65 in human RASFs.Interestingly,Sulf-2 expression positively correlated with the expression of TNF receptor 1,and coimmunoprecipitation assays demonstrated the binding of these two proteins,suggesting they exhibit crosstalk in TNF-αsignaling.This study identified a novel role of Sulf-2 in TNF-αsignaling and the activation of RA synoviocytes,providing the rationale for evaluating the therapeutic targeting of Sulf-2 in preclinical models of RA. | Ruby J.Siegel Anil K.Singh Paul M.Panipinto Farheen S.Shaikh Judy Vinh Sang U.Han H.Mark Kenney Edward M.Schwarz Cynthia S.Crowson Sadik A.Khuder Basil S.Khuder David A.Fox Salahuddin Ahmed | 2022 | Cellular & Molecular Immunology2022，19，10： | 0 |
| 9 | 儿童早期发展前沿研究(上)---早期经验、脑发展和儿童早期教育显示文摘生命早期对形成适应性的脑和行为发展十分重要,关于这一话题存在着很多争议和讨论。儿童是未来的科学家、工人和教育家,为他们提供最佳的发展和学习环境是个非常关键的社会问题。在这个报告中,我将简要地介绍早期经验对脑与行为发展的影响, | Nathan A.Fox | 2014 | 中国科技教育2014，，7： | 0 |
| 10 | 发育过程中的环境烟草烟雾暴露改变行为并扰乱线粒体能量代谢显示文摘[背景]环境烟草烟雾(ETS)暴露与发育缺陷和疾病相关,已知包括影响小脑的功能。然而,直接的生物学效应及内在的神经化学机制仍不清楚。[目的]明确并评估在大鼠小脑发育的关键时期,ETS暴露所导致的潜在神经化学变化。[方法]将出生后第8天(PD8)到第PD23的大鼠,每天暴露于ETS(总悬浮颗粒浓度为300、100和0μg/m3),然后测定行为、神经蛋白质组和细胞水平的反应。[结果]产后ETS暴露诱导在新环境中的运动反应升高,等同于安非他明刺激诱发的效果。ETS暴露大鼠小脑的线粒体亚蛋白质组明显受到干扰。研究结果显示,呈剂量依赖性的需氧过程上调是通过修饰和增加HK1转运至线粒体,伴随ATP合成酶表达的相应提高。ETS暴露也诱导总Dnm1l线粒体分裂因素呈剂量依赖性增加;虽然发现更活跃的膜结合Dnm1l呈低剂量。Dnm1l激活与线粒体染色更强相关,特别是在分子层,它独立于应力诱导的Bcl-2家族的动态。此外,电子显微镜观察显示,Dnm1l介导的线粒体分裂与生物合成增加而非分裂相关。[结论]出生后小脑发育的关键时期对ETS暴露的影响易感,会导致行为改变。ETS的生物效应部分是因为在通常严格控制的情况下,Dnm1l介导的线粒体活跃应答。这些结果显示环境暴露影响神经系统发育和功能的一种新的机制。 | Brian F.Fuller Diego F.Cortes Miranda K.Landis Hiyab Yohannes Hailey E.Griffin Jillian E.Stafflinger M.Scott Bowers Mark H.Lewis Michael A.Fox Andrew K.Ottens | 2013 | 环境与职业医学2013，30，3： | 0 |
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