2025
A single-cell atlas of circulating immune cells over the first 2 months of age in extremely premature infants
Olaloye O, Gu W, Gehlhaar A, Sabuwala B, Eke C, Li Y, Kehoe T, Farmer R, Gabernet G, Lucas C, Tsang J, Lakhani S, Taylor S, Tseng G, Kleinstein S, Konnikova L. A single-cell atlas of circulating immune cells over the first 2 months of age in extremely premature infants. Science Translational Medicine 2025, 17: eadr0942. PMID: 40043141, DOI: 10.1126/scitranslmed.adr0942.Peer-Reviewed Original ResearchConceptsExtremely premature infantsFull-term infantsT cellsMonths of lifePremature infantsImmune cellsMemory CD4<sup>+</sup> T cellsCD4<sup>+</sup> T cellsMemory-like T cellsAnalysis of immune cellsNaive CD4<sup>+</sup>Peripheral T cell developmentWeeks of gestationCord blood samplesNatural killer cellsT helper 1B cell receptor sequencesT cell developmentCycling T cellsMonths of ageSingle-cell suspensionsAmount of bloodSusceptibility to infectionCD4<sup>+</sup>Killer cellsDendritic cell phagosomes recruit GRASP55 for export of antigen-loaded MHC molecules
Cebrian I, Dinamarca S, Rodríguez M, Priego E, Brouwers N, Barends M, Brunnberg J, Tampé R, Blanchard N, Sancho D, Malhotra V. Dendritic cell phagosomes recruit GRASP55 for export of antigen-loaded MHC molecules. Cell Reports 2025, 44: 115333. PMID: 39955774, PMCID: PMC11861518, DOI: 10.1016/j.celrep.2025.115333.Peer-Reviewed Original ResearchConceptsExogenous antigen presentationDendritic cellsAntigen presentationMHC moleculesBone marrow-derived dendritic cellsBone marrow-derived DCCD4<sup>+</sup> T cellsMHC-IActivated CD8<sup>+</sup>MHC class IIDendritic cell phagosomesMHC II moleculesCD8<sup>+</sup>Peptide-loaded MHC moleculesT cellsExogenous antigensMHC-IIClass IIAntigenEndocytic systemGRASP55Cell surfaceIntracellular transportPlasma membranePresentationDecreased T helper 1 cell function underlies recurrent sinopulmonary infections in the 17q12 deletion syndrome
Shin J, Shin H, Gutierrez A, Yoo N, Par-Young J, Osmani L, Shin M, Sanchez-Lara P, Bucala R, Soffer G, Kang I. Decreased T helper 1 cell function underlies recurrent sinopulmonary infections in the 17q12 deletion syndrome. EBioMedicine 2025, 112: 105578. PMID: 39891996, PMCID: PMC11840234, DOI: 10.1016/j.ebiom.2025.105578.Peer-Reviewed Original ResearchConceptsCD4<sup>+</sup> T cellsRecurrent sinopulmonary infectionsT cell functionRNA-seq analysisT cellsHealthy controlsSinopulmonary infectionsRNA-seqT-betIFN-gFrequency of CD4<sup>+</sup> T cellsCD4<sup>+</sup> T cell functionTh1 transcription factor T-betDeletion syndromeFlow cytometryCompared to age-matched healthy controlsTranscription factor T-betDecreased T-betUrinary tract abnormalitiesAge-matched healthy controlsMultiplex assayDownstream effector cytokinesEffector cytokinesRecurrent infectionsTh17 cytokines
2024
Expression of IL-7RαlowCX3CR1+ CD8+ T Cells and α4β7 Integrin Tagged T Cells Related to Mucosal Immunity in Children with Inflammatory Bowel Disease
Yang D, Kim H, Dinh D, Yang J, Hyun C, Jee Y, Lee N, Shin M, Kang I, Kang K. Expression of IL-7RαlowCX3CR1+ CD8+ T Cells and α4β7 Integrin Tagged T Cells Related to Mucosal Immunity in Children with Inflammatory Bowel Disease. Pediatric Gastroenterology Hepatology & Nutrition 2024, 27: 345-354. PMID: 39563840, PMCID: PMC11570351, DOI: 10.5223/pghn.2024.27.6.345.Peer-Reviewed Original ResearchCD8<sup>+</sup> T cellsPeripheral blood mononuclear cellsCD4<sup>+</sup> T cellsInflammatory bowel diseaseT cellsUlcerative colitis groupCrohn's disease groupEffector memoryColitis groupControl groupEffector memory CD8<sup>+</sup> T cellsMemory CD8<sup>+</sup> T cellsCD8+ T cellsBowel diseaseEM CD8<sup>+</sup> T cellsTrafficking immune cellsDisease groupPathogenesis of ulcerative colitisBlood mononuclear cellsInflamed intestinal mucosaConcentrations of TNF-aIntestinal mucosaSerum levelsT lymphocytesImmune cellsNeoself-antigens are the primary target for autoreactive T cells in human lupus
Mori S, Kohyama M, Yasumizu Y, Tada A, Tanzawa K, Shishido T, Kishida K, Jin H, Nishide M, Kawada S, Motooka D, Okuzaki D, Naito R, Nakai W, Kanda T, Murata T, Terao C, Ohmura K, Arase N, Kurosaki T, Fujimoto M, Suenaga T, Kumanogoh A, Sakaguchi S, Ogawa Y, Arase H. Neoself-antigens are the primary target for autoreactive T cells in human lupus. Cell 2024, 187: 6071-6087.e20. PMID: 39276775, DOI: 10.1016/j.cell.2024.08.025.Peer-Reviewed Original ResearchSystemic lupus erythematosusAutoreactive T cellsT cellsMHC-IISelf-antigensDevelopment of lupus-like diseaseCD4<sup>+</sup> T cellsEpstein-Barr virus reactivationPathogenesis of systemic lupus erythematosusRisk factorsSystemic lupus erythematosus patientsMajor histocompatibility complex class IIHistocompatibility complex class IILupus-like diseaseLupus T cellsHuman lupusGenetic risk factorsVirus reactivationLupus erythematosusAdult micePrimary targetTrigger autoimmunityClass IIPeptide presentationInvariant chainThe amalgam of naive CD4+ T cell transcriptional states is reconfigured by helminth infection to dampen the amplitude of the immune response
Even Z, Meli A, Tyagi A, Vidyarthi A, Briggs N, de Kouchkovsky D, Kong Y, Wang Y, Waizman D, Rice T, De Kumar B, Wang X, Palm N, Craft J, Basu M, Ghosh S, Rothlin C. The amalgam of naive CD4+ T cell transcriptional states is reconfigured by helminth infection to dampen the amplitude of the immune response. Immunity 2024, 57: 1893-1907.e6. PMID: 39096910, PMCID: PMC11421571, DOI: 10.1016/j.immuni.2024.07.006.Peer-Reviewed Original ResearchT cell receptorImmune responseNaive CD4<sup>+</sup> T cellsCD4<sup>+</sup> T cellsIFN-IHelminth infectionsNippostrongylus brasiliensis infectionDecreased immune responseType I interferonNaive TT cellsMemory-likeUnrelated antigensTranscriptional changesExtracellular matrixSPF miceCell receptorsI interferonGerm-freeResponse to certain environmental cuesInfectionMiceFunctional changesCell transcriptional statesTranscriptional heterogeneityNanoparticle Retinoic Acid-Inducible Gene I Agonist for Cancer Immunotherapy
Wang-Bishop L, Wehbe M, Pastora L, Yang J, Kimmel B, Garland K, Becker K, Carson C, Roth E, Gibson-Corley K, Ulkoski D, Krishnamurthy V, Fedorova O, Richmond A, Pyle A, Wilson J. Nanoparticle Retinoic Acid-Inducible Gene I Agonist for Cancer Immunotherapy. ACS Nano 2024, 18: 11631-11643. PMID: 38652829, PMCID: PMC11080455, DOI: 10.1021/acsnano.3c06225.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsTumor microenvironmentLipid nanoparticlesBreast cancerResponse to ICIResponse to immune checkpoint inhibitorsInfiltration of CD8<sup>+</sup>Models of triple-negative breast cancerCD4<sup>+</sup> T cellsInhibition of tumor growthTriple-negative breast cancerRIG-IIonizable lipid nanoparticlesLung metastatic burdenIncrease tumor immunogenicityBreast tumor microenvironmentSignaling in vitroACTLA-4Immunogenic melanomaCheckpoint inhibitorsTumor immunogenicityImmunotherapeutic modalitiesCancer immunotherapyMetastatic burdenAPD-1IL-1 receptor 1 signaling shapes the development of viral antigen-specific CD4+ T cell responses following COVID-19 mRNA vaccination
Park H, Shin M, Shin J, Kim H, Kang B, Par-Young J, Unlu S, Afinogenova Y, Catanzaro J, Young J, Kim M, Lee S, Jeon S, You S, Racke M, Bucala R, Kang I. IL-1 receptor 1 signaling shapes the development of viral antigen-specific CD4+ T cell responses following COVID-19 mRNA vaccination. EBioMedicine 2024, 103: 105114. PMID: 38640835, PMCID: PMC11041015, DOI: 10.1016/j.ebiom.2024.105114.Peer-Reviewed Original ResearchConceptsCD4<sup>+</sup> T cellsCOVID-19 mRNA vaccinesAntigen-specific CD4<sup>+</sup> T cell responsesT cell responsesPrimary antibody deficiencyCD4<sup>+</sup> T cell responsesT cellsIL-1R1MRNA vaccinesIL-1IgG antibodiesAntigen-specific CD4<sup>+</sup> T cellsCD4+ T cell responsesLevels of IL-1R1Human CD4<sup>+</sup> T cellsIL-1 receptor 1Healthy individualsDose of COVID-19 mRNA vaccineAntigen-specific CD4IL-1R1 expressionT cell immunityRepetitive antigenic stimulationCytokines interleukin (IL)-1Immune response to virusesExpression of IL-1R1JAK/STAT signaling pathway affects CCR5 expression in human CD4+ T cells
Wang L, Yukselten Y, Nuwagaba J, Sutton R. JAK/STAT signaling pathway affects CCR5 expression in human CD4+ T cells. Science Advances 2024, 10: eadl0368. PMID: 38507500, PMCID: PMC10954213, DOI: 10.1126/sciadv.adl0368.Peer-Reviewed Original ResearchConceptsCD4<sup>+</sup> T cellsT cellsCCR5 expressionPrimary CD4<sup>+</sup> T cellsCD4+ T cellsHuman CD4+ T cellsHuman primary CD4<sup>+</sup> T cellsGlucocorticoid-regulated kinase 1HIV cure agendaHIV co-receptorsSignaling pathwayCCR5 levelsJAK/STAT inhibitor tofacitinibViremic patientsHIV patientsHIV infectionInhibitor tofacitinibJAK/STAT signaling pathwayCCR5Co-receptorHIVProtein levelsCCR2/CCR5Adverse effectsDown-regulationAlternative substitutions of N332 in HIV-1AD8 gp120 differentially affect envelope glycoprotein function and viral sensitivity to broadly neutralizing antibodies targeting the V3-glycan
Jeffy J, Parthasarathy D, Ahmed S, Cervera-Benet H, Xiong U, Harris M, Mazurov D, Pickthorn S, Herschhorn A. Alternative substitutions of N332 in HIV-1AD8 gp120 differentially affect envelope glycoprotein function and viral sensitivity to broadly neutralizing antibodies targeting the V3-glycan. MBio 2024, 15: e02686-23. PMID: 38470051, PMCID: PMC11005340, DOI: 10.1128/mbio.02686-23.Peer-Reviewed Original ResearchConceptsHIV-1 strainsHIV-1V3-glycanEnv antigensHIV-1 infection <i>inNeutralizing antibodiesHost CD4<sup>+</sup> T cellsCirculating HIV-1 strainsEnvelope glycoproteinCD4<sup>+</sup> T cellsHuman immunodeficiency virus type IHIV-1 envelope glycoproteinBlock HIV-1 infectionHIV-1 Env trimerHIV-1 isolatesHIV-1 infectionGp120 V3 loopTarget of neutralizing antibodiesHIV-1 entryCell surface expressionLevels of cell surface expressionSensitivity to antibodiesN332 glycanSoluble CD4Gp120 sheddingSingle-cell transcriptome landscape of circulating CD4+ T cell populations in autoimmune diseases
Yasumizu Y, Takeuchi D, Morimoto R, Takeshima Y, Okuno T, Kinoshita M, Morita T, Kato Y, Wang M, Motooka D, Okuzaki D, Nakamura Y, Mikami N, Arai M, Zhang X, Kumanogoh A, Mochizuki H, Ohkura N, Sakaguchi S. Single-cell transcriptome landscape of circulating CD4+ T cell populations in autoimmune diseases. Cell Genomics 2024, 4: 100473. PMID: 38359792, PMCID: PMC10879034, DOI: 10.1016/j.xgen.2023.100473.Peer-Reviewed Original ResearchConceptsGene programSingle-cell transcriptomic landscapeSingle-cell datasetsCell subpopulationsTranscriptional programsTranscriptomic characterizationCD4<sup>+</sup> T-cell subpopulationsCD4<sup>+</sup> T cellsCellular heterogeneityT cell subpopulationsAutoimmune diseasesCell heterogeneityT cellsPeripheral CD4<sup>+</sup> T cellsCell populationsCD4+ T cell populationCanonical clustersCellsT cell populationsQualitative alterationsT cell heterogeneityGenesSubpopulationsClinical statusCell frequency
2023
IL‐27 produced during acute malaria infection regulates Plasmodium‐specific memory CD4+ T cells
Macalinao M, Inoue S, Tsogtsaikhan S, Matsumoto H, Bayarsaikhan G, Jian J, Kimura K, Yasumizu Y, Inoue T, Yoshida H, Hafalla J, Kimura D, Yui K. IL‐27 produced during acute malaria infection regulates Plasmodium‐specific memory CD4+ T cells. EMBO Molecular Medicine 2023, 15: emmm202317713. PMID: 37855243, PMCID: PMC10701605, DOI: 10.15252/emmm.202317713.Peer-Reviewed Original ResearchConceptsCD4<sup>+</sup> T cellsT cellsIL-27Malaria infectionCD4<sup>+</sup> T cell responsesCD4<sup>+</sup> T cell subsetsMemory CD4+ T cellsImmune responseCD4+ T cellsNeutralization of IL-27T cell responsesT cell subsetsPathogenic immune responsesHumoral immune responseSingle-cell RNA-seq analysisPlasmodium chabaudiDevelopment of vaccinesAcute infectionCytokine productionEffector responsesChronic phaseActive infectionProliferative capacityAcute phaseInfectionExtrafollicular IgD−CD27−CXCR5−CD11c− DN3 B cells infiltrate inflamed tissues in autoimmune fibrosis and in severe COVID-19
Allard-Chamard H, Kaneko N, Bertocchi A, Sun N, Boucau J, Kuo H, Farmer J, Perugino C, Mahajan V, Murphy S, Premo K, Diefenbach T, Ghebremichael M, Yuen G, Kotta A, Akman Z, Lichterfeld M, Walker B, Yu X, Moriyama M, Maehara T, Nakamura S, Stone J, Padera R, Pillai S. Extrafollicular IgD−CD27−CXCR5−CD11c− DN3 B cells infiltrate inflamed tissues in autoimmune fibrosis and in severe COVID-19. Cell Reports 2023, 42: 112630. PMID: 37300833, PMCID: PMC10227203, DOI: 10.1016/j.celrep.2023.112630.Peer-Reviewed Original ResearchConceptsB cell subsetsB-cell depletionIgG4-related diseaseB cellsSevere COVID-19Autoimmune diseasesDouble-negative B cellsPathogenic B cell subsetsCD4<sup>+</sup> T cellsTherapeutic B cell depletionAutoimmune fibrotic diseasesT cellsTissue inflammationInflamed tissuesLung lesionsImmunoglobulin DFibrosisFibrotic diseasesInflammationLesionsDiseaseCOVID-19DN3SubsetsDisease lesions
2022
Type 2 immune polarization is associated with cardiopulmonary disease in preterm infants
Lao J, Bui C, Pang M, Cho S, Rudloff I, Elgass K, Schröder J, Maksimenko A, Mangan N, Starkey M, Skuza E, Sun Y, Beker F, Collins C, Kamlin O, König K, Malhotra A, Tan K, Theda C, Young M, McLean C, Wilson N, Sehgal A, Hansbro P, Pearson J, Polo J, Veldman A, Berger P, Nold-Petry C, Nold M. Type 2 immune polarization is associated with cardiopulmonary disease in preterm infants. Science Translational Medicine 2022, 14: eaaz8454. PMID: 35385341, DOI: 10.1126/scitranslmed.aaz8454.Peer-Reviewed Original ResearchConceptsPreterm infantsBronchopulmonary dysplasiaIL-13CD3<sup>+</sup>CD4<sup>+</sup> T cellsInterleukin-4BPD-associated pulmonary hypertensionMaternal magnesium sulfate therapyCD4<sup>+</sup> T cellsCardiopulmonary diseaseMagnesium sulfate therapyType 2 mediatorsHealthy term infantsType 2 polarizationType 2 cytokinesHepatitis B vaccineMultiple therapeutic approachesTerm infantsPulmonary hypertensionDisease in vivoT cellsLung inflammationYounger patientsIL-5B vaccineHigh treatment costs
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