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CD4^(+)T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors

Cellular & Molecular Immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël C.de Groot Marij J.P.Welters Tom de Wit ellen Schrama Hans van eenennaam Saskia J.Santegoets Timo Oosenbrug Annemarthe van der Veen Joris L.Vos Charlotte L.Zuur Noel F.C.C.de Miranda Heinz Jacobs Sjoerd H.van der Burg jannie Borst Yanling Xiao Department of Immunology Leiden University Medical CenterLeidenThe Netherlands Oncode Institute Leiden University Medical CenterLeidenThe Netherlands Department of Tumor Biology and Immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS B.V. OssThe Netherlands Division of Medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Otorhinolaryngology Leiden University Medical Center LeidenThe Netherlands Department of Pathology Leiden University Medical CenterLeidenThe Netherlands

CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse *** recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting ***,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in *** CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer *** cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response ***-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T *** agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TMe is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： CD4^(+)T-cell help cDC1 licensing IFN-I signaling CD40 costimulation (cross-)presentation CTL priming Tumor control

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Inflammatory pathways of importance for management of inflammatory bowel disease

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World Journal of Gastroenterology 2014年第1期20卷 64-77页

作者： jannie.pe.e.se. Mehmet Coskun Christoffer Soendergaard Mohammad Salem Ole Haagen Nielsen Department of Gastroenterology Medical SectionUniversity of CopenhagenHerlev HospitalDK-2730 HerlevDenmark Department of Cellular and Molecular Medicine the Panum InstituteUniversity of CopenhagenDK-2200 CopenhagenDenmark

Inflammatory bowel disease(IBD)is a group of chronic disorders of the gastrointestinal tract comprising Crohn’s disease(CD)and ulcerative colitis(UC).Their etiologies are unknown,but they are characterised by an imbalanced production of pro-inflammatory mediators,e.g.,tumor necrosis factor(TNF)-α,as well as increased recruitment of leukocytes to the site of *** in understanding the role of the inflammatory pathways in IBD and an inadequate response to conventional therapy in a large portion of patients,has over the last two decades lead to new therapies which includes the TNF inhibitors(TNFi),designed to target and neutralise the effect of TNF-α.TNFi have shown to be efficient in treating moderate to severe CD and ***,convenient alternative therapeutics targeting other immune pathways are needed for patients with IBD refractory to conventional therapy including ***,several therapeutics are currently under development,and have shown success in clinical *** include antibodies targeting and neutralising interleukin-12/23,small pharmacologic Janus kinase inhibitors designed to block intracellular signaling of several pro-inflammatory cytokines,antibodies targeting integrins,and small anti-adhesion molecules that block adhesion between leukocytes and the intestinal vascular endothelium,reducing their infiltration into the inflamed *** this review we have elucidated the major signaling pathways of clinical importance for IBD therapy and highlighted the new promising therapies *** stated in this paper several new treatment options are under development for the treatment of CD and UC,however,no drug fits all ***,optimisations of treatment regimens are warranted for the benefit of the patients either through biomarker establishment or other rationales to maximise the effect of the broad range of mode-of-actions of the present and future drugs in IBD.

关键词： Anti-tumor necrosis factor Biologics Crohn’s disea

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Prophylactic Antibiotic Treatment during Hysteroscopy: A Systematic Review

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Open Journal of Obstetrics and Gynecology 2015年第3期5卷 163-166页

作者： jannie Wijma Paul J. Q. van der Linden Deventer Ziekenhuis Deventer The Netherlands

Background: Overall, the use of antibiotics is increasing. We noticed different practices amongst different hospitals in their prophylactic use of antibiotics during operative hysteroscopy. This review investigates whether there is sufficient evidence to recommend antibiotic prophylaxis in operative hysteroscopy. Methods: We performed a systematic search in “Pubmed” using “hysteroscopy” and “antibiotic” and “prophylaxis” as search items. We found 16 hits of which 4 were suitable to include in our review. Findings: In an included Cochrane review no conclusion was drawn since no articles could be included. A prospective study by Nappi?et al.?[1]?support the recommendation of the American College of Obstetricians and Gynaecologists not to prescribe routinely antibiotic prophylaxis in cases of hysteroscopic surgery. Bhattacharya?et al. conducted a prospective study that was ended prematurely. They conclude that there is no convincing evidence that prophylactic antibiotics are of value in hysteroscopy. A review by Morrill?et al. yielded no new data. Conclusion: We did not find a significant increase in clinical relevant infectious symptoms after hysteroscopy in women treated with or without antibiotic prophylaxis, although data are insufficient to draw a definite conclusion. Therefore, we suggest a prospective study is mandatory on this topic.

关键词： Antibiotic Prophylaxis Operative Hysteroscopy

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霸气灵魂

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当代体育（扣篮） 2004年第48期 9-9页

作者：程凭余 jannie 哈尔滨市南岗区学府四道街军队离退休干部第一休养所

似乎,只有在夕阳抹向天边烈烈的血红时,人们才能想起他;似乎,只有在惊雷震向大地兢兢的颤抖时,人们才能想起他;似乎,只有在暴雨扫向池塘啪啪的水花时,人们才会想起他。想起他的火烈,想起他的威慑,想起他的震撼,想起他的霸气灵魂。肯扬... 详细信息

似乎,只有在夕阳抹向天边烈烈的血红时,人们才能想起他;似乎,只有在惊雷震向大地兢兢的颤抖时,人们才能想起他;似乎,只有在暴雨扫向池塘啪啪的水花时,人们才会想起他。想起他的火烈,想起他的威慑,想起他的震撼,想起他的霸气灵魂。肯扬·马丁是一个很有意思的球员,吸引我注意的,不是他场场系在头上的红色发带,不是他时时传出的大声怒吼,更不是他东部劲旅网队的帽子,而是他的大力扣篮,强热灌筐,还有左手臂上的汉字文身——患得患失。

关键词：网队左手臂花时艾弗森新泽西网篮球比赛莎拉波娃总冠军雷震一语道破天机

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CD70 defines a subset of proinflammatory and CNSpathogenic TH1/TH17 lymphocytes and is overexpressed in multiple sclerosis

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Cellular & Molecular Immunology 2019年第7期16卷 652-665页

作者： Tessa Dhaeze Laurence Tremblay Catherine Lachance evelyn peelen Stephanie Zandee Camille Grasmuck Lyne Bourbonnière Sandra Larouche Xavier Ayrignac Rose-Marie Rébillard Josée Poirier Boaz Lahav Pierre Duquette Marc Girard Robert Moumdjian Alain Bouthillier Catherine Larochelle Alexandre Prat Department of Neuroscience Faculty of MedicineUniversitéde Montréaland Centre de Recherche du CHUM(CRCHUM)MontréalQC H2X0A9Canada Multiple Sclerosis Clinic Division of NeurologyCHUMMontréalQC H2X0A9Canada Division of Neurosurgery CHUMMontréalQC H2X0A9Canada CD70 is the unique ligand of CD27 and is expressed on immune cells only upon

***,engagement of the costimulatory CD27/CD70 pathway is solely dependent on upregulation of ***,the T cell-intrinsic effect and function of human CD70 remain ***,we describe that CD70 expression distinguishes proinflammatory CD4^(+)T lymphocytes that display an increased potential to migrate into the central nervous system(CNS).Upregulation of CD70 on CD4^(+)T lymphocytes is induced by TGF-β1 and TGF-β3,which promote a pathogenic *** addition,CD70 is associated with a TH1 and TH17 profile of lymphocytes and is important for T-bet and IFN-γexpression by both T helper ***,adoptive transfer of CD70−/−CD4^(+)T lymphocytes induced less severe experimental autoimmune encephalomyelitis(eAe)disease than transfer of WT CD4^(+)T ***70+CD4^(+)T lymphocytes are found in the CNS during acute autoimmune inflammation in humans and mice,highlighting CD70 as both an immune marker and an important costimulator of highly pathogenic proinflammatory TH1/TH17 lymphocytes infiltrating the CNS.

关键词： CD70+CD4^(+)T lymphocytes multiple sclerosis CD27/CD70 pathway TGF-β1 TGF-β3 soluble CD70 blood-brain barrier endothelial cells experimental autoimmune encephalitis TCR1640 transgene mouse model

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