Featured Publications
Regulatory T cells function in established systemic inflammation and reverse fatal autoimmunity
Hu W, Wang Z, Feng Y, Schizas M, Hoyos B, van der Veeken J, Verter J, Bou-Puerto R, Rudensky A. Regulatory T cells function in established systemic inflammation and reverse fatal autoimmunity. Nature Immunology 2021, 22: 1163-1174. PMID: 34426690, PMCID: PMC9341271, DOI: 10.1038/s41590-021-01001-4.Peer-Reviewed Original ResearchConceptsRegulatory T cellsTreg cellsFatal autoimmune diseaseSystemic inflammationAutoimmune diseasesT cellsPro-inflammatory effector cellsFatal autoimmune inflammationFOXP3 protein expressionSevere tissue inflammationTranscription factor Foxp3Autoimmune inflammationFatal autoimmunityInflammatory mediatorsEffector cellsImmune activationImmunosuppressive functionTissue inflammationDiseased miceImmune homeostasisInflammatory responseFactor Foxp3Long-term protectionInflammationLoss of functionExpression of Foxp3 by T follicular helper cells in end-stage germinal centers
Jacobsen J, Hu W, R Castro T, Solem S, Galante A, Lin Z, Allon S, Mesin L, Bilate A, Schiepers A, Shalek A, Rudensky A, Victora G. Expression of Foxp3 by T follicular helper cells in end-stage germinal centers. Science 2021, 373 PMID: 34437125, PMCID: PMC9007630, DOI: 10.1126/science.abe5146.Peer-Reviewed Original ResearchConceptsFollicular helper cellsGerminal centersHelper cellsFormation of GCsExpression of Foxp3Effective antibody responseTranscription factor Foxp3Acute surgeAntibody responseFactor Foxp3T cellsFoxp3Immunoglobulin somatic hypermutationGC sizeAffinity maturationPotential regulatorCellsEctopic expressionSomatic hypermutationExpressionAntibodiesDifferential outcome of TRIF-mediated signaling in TLR4 and TLR3 induced DC maturation.
Hu W, Jain A, Gao Y, Dozmorov IM, Mandraju R, Wakeland EK, Pasare C. Differential outcome of TRIF-mediated signaling in TLR4 and TLR3 induced DC maturation. Proc Natl Acad Sci U S A 2015, 112: 13994-9. PMID: 26508631, DOI: 10.1073/pnas.1510760112.Peer-Reviewed Original ResearchIRAK-1 bypasses priming and directly links TLRs to rapid NLRP3 inflammasome activation.
Lin KM, Hu W, Troutman TD, Jennings M, Brewer T, Li X, Nanda S, Cohen P, Thomas JA, Pasare C. IRAK-1 bypasses priming and directly links TLRs to rapid NLRP3 inflammasome activation. Proc Natl Acad Sci U S A 2014, 111: 775-80. PMID: 24379360, DOI: 10.1073/pnas.1320294111.Peer-Reviewed Original ResearchPriming microenvironments dictate cytokine requirements for T helper 17 cell lineage commitment.
Hu W, Troutman TD, Edukulla R, Pasare C. Priming microenvironments dictate cytokine requirements for T helper 17 cell lineage commitment. Immunity 2011, 35: 1010-22. PMID: 22137454, DOI: 10.1016/j.immuni.2011.10.013.Peer-Reviewed Original Research
2023
Distinct metabolic requirements regulate B cell activation and germinal center responses
Sharma R, Smolkin R, Chowdhury P, Fernandez K, Kim Y, Cols M, Alread W, Yen W, Hu W, Wang Z, Violante S, Chaligné R, Li M, Cross J, Chaudhuri J. Distinct metabolic requirements regulate B cell activation and germinal center responses. Nature Immunology 2023, 1-12. PMID: 37365386, DOI: 10.1038/s41590-023-01540-y.Peer-Reviewed Original ResearchNaïve B cellsB cellsGerminal centersB cell-dependent immune responsesExtrafollicular B cell responsesCell-dependent immune responsesB cell responsesGerminal center responseB cell activationMetabolic requirementsAntibody responseDistinct metabolic requirementsHigh-affinity antibodiesT cellsExtrafollicular sitesImmune responseProliferating lymphocytesCenter responseClonal proliferationCell activationCell responsesGC reactionLactate dehydrogenaseAerobic glycolysisNaïveConserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs new combination cancer therapy strategies
Glasner A, Rose S, Sharma R, Gudjonson H, Chu T, Green J, Rampersaud S, Valdez I, Andretta E, Dhillon B, Schizas M, Dikiy S, Mendoza A, Hu W, Wang Z, Chaudhary O, Xu T, Mazutis L, Rizzuto G, Quintanal-Villalonga A, Manoj P, de Stanchina E, Rudin C, Pe’er D, Rudensky A. Conserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs new combination cancer therapy strategies. Nature Immunology 2023, 24: 1020-1035. PMID: 37127830, PMCID: PMC10232368, DOI: 10.1038/s41590-023-01504-2.Peer-Reviewed Original ResearchConceptsTreg cell depletionRegulatory T cellsT cellsCell depletionEffector T cellsInjury-induced inflammationTreg cell functionSolid organ cancersAntigen presenting cellsExperimental lung cancerLung adenocarcinoma progressionAccessory cell typesT cell activationRational combination treatmentsTreg cellsCorresponding monotherapiesOrgan cancersLung cancerInjury settingPresenting cellsVEGF blockadeAdenocarcinoma progressionCombination treatmentMyeloid cellsCell activation
2022
Genetic tracing reveals transcription factor Foxp3-dependent and Foxp3-independent functionality of peripherally induced Treg cells
van der Veeken J, Campbell C, Pritykin Y, Schizas M, Verter J, Hu W, Wang Z, Matheis F, Mucida D, Charbonnier L, Chatila T, Rudensky A. Genetic tracing reveals transcription factor Foxp3-dependent and Foxp3-independent functionality of peripherally induced Treg cells. Immunity 2022, 55: 1173-1184.e7. PMID: 35700740, PMCID: PMC9885886, DOI: 10.1016/j.immuni.2022.05.010.Peer-Reviewed Original ResearchConceptsPTreg cellsTranscription factor Foxp3Treg cellsFactor Foxp3Absence of Foxp3Foxp3-independent mannerPeripheral Treg cellsRegulatory T cellsRole of Foxp3Genetic tracingSuppress autoimmunityTolerogenic signalsEffector TT cellsFoxp3Mature CD4Commensal microbiotaCell lineagesCellsCell expansionCell programTTregsColitisCD4Autoimmunity
2020
The Transcription Factor Foxp3 Shapes Regulatory T Cell Identity by Tuning the Activity of trans-Acting Intermediaries
van der Veeken J, Glasner A, Zhong Y, Hu W, Wang Z, Bou-Puerto R, Charbonnier L, Chatila T, Leslie C, Rudensky A. The Transcription Factor Foxp3 Shapes Regulatory T Cell Identity by Tuning the Activity of trans-Acting Intermediaries. Immunity 2020, 53: 971-984.e5. PMID: 33176163, PMCID: PMC8363055, DOI: 10.1016/j.immuni.2020.10.010.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoimmune DiseasesAutoimmunityBinding SitesChromatin Assembly and DisassemblyDisease Models, AnimalEpigenesis, GeneticFemaleForkhead Transcription FactorsGene Expression RegulationImmunohistochemistryMaleMiceNucleotide MotifsOrgan SpecificityProtein BindingT-Lymphocytes, RegulatoryTrans-ActivatorsConceptsRegulatory T Cell IdentityChromatin accessibilityCell identityT cell identityDNA sequence motifsGene expression patternsMajor chromatinChromatin regionsTF bindingSequence motifsTCF7 geneEpigenetic featuresGenetic variationNegative regulationNull allelesExpression patternsPresence of DNATreg cell identityFOXP3 functionTCF1MotifIndirect mannerCellsTranscription factor Foxp3Chromatin
2016
ARC Syndrome-Linked Vps33B Protein Is Required for Inflammatory Endosomal Maturation and Signal Termination.
Akbar MA, Mandraju R, Tracy C, Hu W, Pasare C, Krämer H. ARC Syndrome-Linked Vps33B Protein Is Required for Inflammatory Endosomal Maturation and Signal Termination. Immunity 2016, 45: 267-79. PMID: 27496733, DOI: 10.1016/j.immuni.2016.07.010.Peer-Reviewed Original Research
2013
Enhancement of anti-tumor CD8 immunity by IgG1-mediated targeting of Fc receptors
Furlan SN, Mandraju R, Brewer T, Roybal K, Troutman TD, Hu W, Palm NW, Unni A, Pasare C. Enhancement of anti-tumor CD8 immunity by IgG1-mediated targeting of Fc receptors. MAbs 2013, 6: 108-118. PMID: 24284965, PMCID: PMC3929435, DOI: 10.4161/mabs.27052.Peer-Reviewed Original ResearchConceptsT cell responsesFc receptorsTumor cellsT cellsAnti-tumor T cell responsesCell responsesEffective anti-tumor responseAnti-tumor CD8DC vaccine strategiesDendritic cell functionTumor-derived antigensAnti-tumor responseTumor-specific antigensFc regionTherapeutic tumor vaccinesInnate immune responseIgG1 Fc regionSuch tumor cellsSurface of tumorVariety of receptorsProfessional antigenTumor vaccinesVaccine strategiesAntigen uptakePrimary tumorLocation, location, location: tissue-specific regulation of immune responses.
Hu W, Pasare C. Location, location, location: tissue-specific regulation of immune responses. J Leukoc Biol 2013, 94: 409-21. PMID: 23825388, DOI: 10.1189/jlb.0413207.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2012
Role for B-cell adapter for PI3K (BCAP) as a signaling adapter linking Toll-like receptors (TLRs) to serine/threonine kinases PI3K/Akt.
Troutman TD, Hu W, Fulenchek S, Yamazaki T, Kurosaki T, Bazan JF, Pasare C. Role for B-cell adapter for PI3K (BCAP) as a signaling adapter linking Toll-like receptors (TLRs) to serine/threonine kinases PI3K/Akt. Proc Natl Acad Sci U S A 2012, 109: 273-8. PMID: 22187460, DOI: 10.1073/pnas.1118579109.Peer-Reviewed Original Research
2007
Solution structure and backbone dynamics of an endopeptidase HycI from Escherichia coli: implications for mechanism of the [NiFe] hydrogenase maturation.
Yang F, Hu W, Xu H, Li C, Xia B, Jin C. Solution structure and backbone dynamics of an endopeptidase HycI from Escherichia coli: implications for mechanism of the [NiFe] hydrogenase maturation. J Biol Chem 2007, 282: 3856-63. PMID: 17150961, DOI: 10.1074/jbc.M609263200.Peer-Reviewed Original Research
2006
The solution structure of Escherichia coli Wzb reveals a novel substrate recognition mechanism of prokaryotic low molecular weight protein-tyrosine phosphatases.
Lescop E, Hu Y, Xu H, Hu W, Chen J, Xia B, Jin C. The solution structure of Escherichia coli Wzb reveals a novel substrate recognition mechanism of prokaryotic low molecular weight protein-tyrosine phosphatases. J Biol Chem 2006, 281: 19570-7. PMID: 16651264, DOI: 10.1074/jbc.M601263200.Peer-Reviewed Original Research