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A key role for PTP1B in dendritic cell maturation, migration, and T cell activation

分子细胞生物学报:英文版 2015年第6期7卷 517-528页

作者： Cristina Martin-Granados Alan R.Prescott Samantha Le Sommer Izabela P.Klaska Tian Yu Elizabeth Muckersie Claudiu V.Giuraniuc Louise Grant Mirela Delibegovic John V.Forrester Institute of Medical Sciences University of AberdeenCollege of Life Sciences and MedicineAberdeen AB252ZDUK Department of Pharmacology University of CambridgeCambridge CB21PDUK Division of cell Biology and Immunology College of Life SciencesUniversity of DundeeDundee DD15EHUK Centre for Ophthalmology and Visual Science The University of Western AustraliaPerthAustralia Centre for Experimental Immunology Lions Eye InstituteNedlandsWA 6009Australia

dendritic cells(DC)are the major antigen-presenting cells bridging innate and adaptive immunity,a function they perform by converting quiescent DC to active,mature DC with the capacity to activate naı¨ve T *** do this by migrating from the tissues to the T cell area of the secondary lymphoid ***,wedemonstrate thatmyeloid cell-specific genetic deletion of PTP1B(LysM PTP1B)leads to defects in lipopolysaccharide-driven bone marrow-derivedDC(BMDC)activation associated with increased levels of phosphorylated *** showthatmyeloid cell-specific PTP1Bdeletion also causes decreased migratory capacity of epidermal DC,aswell as reduced CCR7 expression and chemotaxis to CCL19 by ***1B deficiency in BMDC also impairs their migration in ***,immature LysM PTP1B BMDC display fewer podosomes,increased levels of phosphorylated Src at tyrosine 527,and loss of Src localization to podosome *** co-culture with T cells,LysM PTP1B BMDC establish fewer and shorter contacts than control ***,LysMPTP1BBMDCfail to present antigen to T cells as efficiently as *** data provide first evidence for a key regulatory role for PTP1B in mediating a central DC function of initiating adaptive immune responses in response to innate immune cell activation.

关键词： dendritic cell maturation podosomes T cell activation adaptive immune response protein tyrosine phosphatase 1B

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A rationally designed cancer vaccine based on NIR-II fluorescence image-guided light-triggered remote control of antigen cross-presentation and autophagy

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药学学报:英文版 2023年第7期13卷 3121-3136页

作者： Aihua Wu Afeng Yang Qinli Tong Guoguang Wei Sihang Zhang Sheng Yu Chen Zhang Jiaojiao Xu Wei Lu School of Pharmacy&Minhang Hospital Key Laboratory of Smart Drug DeliveryMinistry of Education&State Key Laboratory of Molecular Engineering of PolymersFudan UniversityShanghai 201203China

Cancer vaccines represent a promising immunotherapeutic treatment *** promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex(MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side *** vaccination strategies,however,are not able to achieve the spatiotemporal control of antigen ***,we report a liposomal vaccine loading the second near-infrared window(NIR-II,1000—1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging *** NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes(DLNs).Moreover,the photothermally induced endolysosomal rupture initiates *** also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/m TOR *** light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell *** study presents a paradigm of NIR-II image-guided light-triggered *** approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.

关键词： Vaccine Light-triggered NIR-II imaging Cross-presentation Autophagy Simvastatin Endolysosomal escape dendritic cell maturation

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Probiotic metabolites from Bacillus coagulans GanedenBC30^(TM) support maturation of antigen-presenting cells in vitro

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World Journal of Gastroenterology 2012年第16期18卷 1875-1883页

作者： Kathleen F Benson Kimberlee A Redman Steve G Carter David Keller Sean Farmer John R Endres Gitte S Jensen NIS Labs 1437 EsplanadeKlamath FallsOR 97601United States Ganeden Biotech 5915 Landerbrook DriveMayfield HeightsOH 44124United States AIBMR Life Sciences 4117 S MeridianPuyallupWA 98373United States

AIM:To study the effects of probiotic metabolites on maturation stage of antigen-presenting immune ***:Ganeden Bacillus coagulans 30(GBC30) bacterial cultures in log phase were used to isolate the secreted metabolite(MET) fraction.A second fraction was made to generate a crude cell-wall-enriched fraction,by centrifugation and lysis,followed by washing.A preparation of MET was subjected to size exclusion centrifugation,generating three fractions:cell wall in primary cultures of human peripheral blood mononuclear cell(PBMC) as a source of antigen-presenting mononuclear *** maturation status of mononuclear phagocytes was evaluated by staining with monoclonal antibodies towards CD14,CD16,CD80 and CD86 and analyzed by flow ***:Treatment of PBMC with MET supported maturation of mononuclear phagocytes toward both macrophage and dendritic cell *** biological activity unique to the metabolites included a reduction of CD14+ CD16+ pro-inflammatory cells,and this property was associated with the high molecular weight metabolite *** were also seen for the dendritic cell maturation markers CD80 and *** CD14dim cells,an increase in both CD80 and CD86 expression was seen,in contrast to a selective increase in CD86 expression on CD14bright *** co-expression of CD80 and CD86 indicates effective antigen presentation to T cells and support of T helper cell *** selective expression of CD86 in the absence of CD80 points to a role in generating T regulatory ***:The data show that a primary mechanism of action of GBC30 metabolites involves support of more mature phenotypes of antigen-presenting cells,important for immunological decision-making.

关键词： Mononuclear phagocytes dendritic cell maturation Co-stimulatory molecules Antigen-presentation Probiotics Metabolites

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