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The chemokine receptor CCR7 is a promising target for rheumatoid arthritis therapy

Cellular & Molecular Immunology 2019年第10期16卷 791-799页

作者： Georgios L.Moschovakis Anja Bubke michaela friedrichsen Jasmin Ristenpart Jaap Willem Back Christine S.Falk Elisabeth Kremmer Reinhold Forster Institute of Immunology Hannover Medical SchoolCarl-Neuberg Str.130625 HannoverGermany Pepscan Therapeutics BV LelystadThe Netherlands Institute of Transplant Immunology Integrated Research and Treatment Center TransplantationIFB.TxHannover Medical SchoolCarl-Neuberg Str.130625 HannoverGermany Helmholtz-Zentrum München Institute of Molecular ImmunologyD-81377 MunichGermany Present address:Biozentrum Martinsried Dept.Bio II.LMU MünchenGrosshaderner Str.2D-82152 MartinsriedGermany

The chemokine receptor CCR7 and its ligands CCL19 and CCL21 guide the homing and positioning of dendritic and T cells in lymphoid organs,thereby contributing to several aspects of adaptive immunity and immune *** the present study,we investigated the role of CCR7 in the pathogenesis of collagen-induced arthritis(CIA).By using a novel anti-human CCR7 antibody and humanized CCR7 mice,we evaluated CCR7 as a target in this autoimmune model of rheumatoid arthritis(RA).Ccr7-deficient mice were completely resistant to CIA and presented severely impaired antibody responses to collagen II(CII).Selective CCR7 expression on dendritic cells restored arthritis severity and anti-CII antibody *** and therapeutic treatment of humanized CCR7 mice with anti-human CCR7 mAb 8H3-16A12 led to complete resistance to CIA and halted CIA progression,*** data demonstrate that CCR7 signaling is essential for the induction of CIA and identify CCR7 as a potential therapeutic target in RA.

关键词： CCR7 impaired immunity

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Neutralization of the SARS-CoV-2 Delta variant after heterologous and homologous BNT162b2 or ChAdOx1 nCoV-19 vaccination

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Cellular & Molecular Immunology 2021年第10期18卷 2455-2456页

作者： Swantje I.Hammerschmidt Berislav Bosnjak Günter Bernhardt michaela friedrichsen Inga Ravens Alexandra Dopfer-Jablonka Markus Hoffmann Stefan Pöhlmann Georg M.N.Behrens Reinhold Förster Institute of Immunology Hannover Medical SchoolHannoverGermany Department for Rheumatology and Immunology Hannover Medical SchoolHannoverGermany Infection Biology Unit German Primate Center-Leibniz Institute for Primate ResearchGöttingenGermany Faculty of Biology and Psychology Georg-August-University GöttingenGöttingenGermany German Center for Infection Research(DZIF) Partner Site Hannover-BraunschweigHannoverGermany German Center for Lung Research(DZL) HannoverGermany Cluster of Excellence RESIST(EXC 2155) Hannover Medical SchoolHannoverGermany

Since the beginning of the COVID-19 pandemic,divergent variants of concern(VoCs)of SARS-CoV-2 have evolved and become the most prevalent SARS-CoV-2 variants in distinct locations at different ***,the Delta variant(B.1.617.2)dominates infection events in large parts of the *** campaigns,however,still use SARS-CoV-2 vaccines based on the spike(S)protein of the original Wuhan virus.

关键词： Delta homologous campaign

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Efficient IL-2R signaling differentially affects the stability,function,and composition of the regulatory T-cell pool

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Cellular & Molecular Immunology 2021年第2期18卷 398-414页

作者： Marc Permanyer Berislav Bošnjak Silke Glage michaela friedrichsen Stefan Floess Jochen Huehn Gwendolyn E.Patzer Ivan Odak Nadine Eckert Razieh Zargari Laura Ospina-Quintero Hristo Georgiev Reinhold Förster Institute of Immunology Hannover Medical SchoolHannoverGermany Institute for Laboratory Animal Science Hannover Medical SchoolHannoverGermany Department Experimental Immunology Helmholtz Centre for Infection ResearchBraunschweigGermany Cluster of Excellence RESIST(EXC 2155) Hannover Medical School30625HannoverGermany

Signaling via interleukin-2 receptor(IL-2R)is a requisite for regulatory T(Treg)cell identity and ***,it is not completely understood to what degree IL-2R signaling is required for Treg cell homeostasis,lineage stability and function in both resting and inflammatory ***,we characterized a spontaneous mutant mouse strain endowed with a hypomorphic Tyr129His variant of CD25,theα-chain of IL-2R,which resulted in diminished receptor expression and reduced IL-2R *** noninflammatory conditions,Cd25Y129H mice harbored substantially lower numbers of peripheral Treg cells with stable Foxp3 expression that prevented the development of spontaneous autoimmune *** contrast,Cd25^(Y^(129H))Treg cells failed to efficiently induce immune suppression and lost lineage commitment in a T-cell transfer colitis model,indicating that unimpaired IL-2R signaling is critical for Treg cell function in inflammatory ***,single-cell RNA sequencing of Treg cells revealed that impaired IL-2R signaling profoundly affected the balance of central and effector Treg cell ***,partial loss of IL-2R signaling differentially interferes with the maintenance,heterogeneity,and suppressive function of the Treg cell pool.

关键词： Regulatory T cells IL-2R signaling scRNA sequencing Treg heterogeneity

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