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Retinoic acid signaling acts as a rheostat to balance Treg function

Cellular & Molecular Immunology 2022年第7期19卷 820-833页

作者： Govindarajan Thangavelu Gabriela Andrejeva Sara Bolivar-Wagers Sujeong Jin Michael C.Zaiken Michael Loschi Ethan G.Aguilar Scott N.Furlan Chrysothemis C.Brown Yu-Chi Lee Cameron McDonald hyman Colby J.Feser Angela Panoskaltsis-Mortari Keli L.hippen Kelli P.MacDonald William J.Murphy Ivan Maillard Geoffrey R.hill david h.munn Robert Zeiser Leslie S.Kean Jeffrey C.Rathmell hongbo Chi Randolph J.Noelle Bruce R.Blazar Department of Pediatrics Center for ImmunologyUniversity of MinnesotaMinneapolisMNUSA Center for Immunobiology Vanderbilt University Medical CenterNashville TNUSA Department of Pediatrics University of WashingtonSeattleWAUSA Fred hutchinson Cancer Research Center SeattleWAUSA howard hughes Medical Institute Immunology Program and Ludwig CenterSloan Kettering InstituteMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Department of Microbiology and Immunology.Geisel School of Medicine at Dartmouth Norris Cotton Cancer CenterLebanonUSA Department of Immunology Queensland Institute of Medical Research(QIMR)Berghofer Medical Research Institute and School of MedicineUniversity of QueenslandBrisbaneQLDAustralia Departmentof Dermatology School of MedicineUniversity of California DavisSacramentoCAUSA Division of hematology/Oncology Department of MedicineUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaPAUSA Georgia Cancer Center Augusta UniversityAugustaGAUSA Department of haematology Oncology and Stem Cell TransplantationFaculty of MedicineFreiburg University Medical CentreFreiburgGermany Boston Children's hospital and the Dana-Farber Cancer Institute BostonMAUSA Department of Immunology St.Jude Children's ResearchHospitalMemphisTNUSA

Regulatory T cells(Tregs)promote immune homeostasis by maintaining self-tolerance and regulating inflammatory *** certain inflammatory conditions,Tregs can lose their lineage stability and *** studies have reported that ex vivo exposure to retinoic acid(RA)enhances Treg function and ***,it is unknown how RA receptor signaling in Tregs influences these processes in ***,we employed mouse models in which RA signaling is silenced by the expression of the dominant negative receptor(DN)RARαin all T *** the fact that DNRARαconventional T cells are hypofunctional,Tregs had increased CD25 expression,STAT5 pathway activation,mTORC1 signaling and supersuppressor ***,DNRARαTregs had increased inhibitory molecule expression,amino acid transporter expression,and metabolic fitness and decreased antiapoptotic *** function was observed when wild-type mice were treated with a pharmacologic pan-RAR ***,Treg-specific expression of DNRARαresulted in distinct phenotypes,such that a single allele of DNRARαin Tregs heightened their suppressive function,and biallelic expression led to loss of suppression and *** loss of Treg function was not cell intrinsic,as Tregs that developed in a noninflammatory milieu in chimeric mice reconstituted with DNRARαand wild-type bone marrow maintained the enhanced suppressive *** mapping suggested that maintaining Treg stability in an inflammatory milieu requires RA *** findings indicate that RA signaling acts as a rheostat to balance Treg function in inflammatory and noninflammatory conditions in a dose-dependent manner.

关键词： Retinoic acid Tregulatory cells Autoimmunity Metabolism mTORC1 STAT5

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Abscisic Acid Connects Phytohormone Signaling with RNA Metabolic Pathways and Promotes an Antiviral Response that Is Evaded by a Self- Controlled RNA Virus

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Plant Communications 2020年第5期1卷 111-128页

作者： Fabio Pasin hongying Shan Beatriz García Maren Müller david San León Márta Ludman david h.Fresno Károly Fátyol Sergi munné-Bosch Guillermo Rodrigo Juan Antonio García Centro Nacional de Biotecnología(CNB-CSIC) 28049 MadridSpain Agricultural Biotechnology Research Center Academia Sinica11529 TaipeiTaiwan Departamento de Biologı´a Evolutiva Ecologı´a y Ciencias AmbientalesFacultad de Biologı´aUniversidad de Barcelona08028 BarcelonaSpain Agricultural Biotechnology Institute National Agricultural Research and Innovation Centre2100 Godoll}oHungary Institute for Integrative Systems Biology(I2SysBio) CSIC-University of Valencia46980 PaternaSpain Present address:College of horticulture and Gardening Tianjin Agricultural University300384 TianjinChina

A complex network of cellular receptors,RNA targeting pathways,and small-molecule signaling provides robust plant immunity and tolerance to *** maximize their fitness,viruses must evolve control mechanisms to balance host immune evasion and plant-damaging *** genus Potyvirus comprises plant viruses characterized by RNA genomes that encode large polyproteins led by the P1 protease.A P1 autoinhibitory domain controls polyprotein processing,the release of a downstream functional RNAsilencing suppressor,and viral ***,we show that P1Pro,a plum pox virus clone that lacks the P1 autoinhibitory domain,triggers complex reprogramming of the host transcriptome and high levels of abscisic acid(ABA)accumulation.A meta-analysis highlighted ABA connections with host pathways known to control RNA stability,turnover,maturation,and *** changes triggered by P1Pro infection or ABA showed similarities in host RNA abundance and *** and hormone treatment assays showed that ABA promotes plant resistance to potyviral ***,quantitative mathematical modeling of viral replication in the presence of defense pathways supported self-control of polyprotein processing kinetics as a viral mechanism that attenuates the magnitude of the host antiviral ***,our findings indicate that ABA is an active player in plant antiviral immunity,which is nonetheless evaded by a self-controlled RNA virus.

关键词： abscisic acid antiviral immune evasion mathematical modeling viral polyprotein processing Potyvirus RNA metabolism

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