Featured Publications
Single-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
2024
Neoself-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 chainSpatial transcriptomics elucidates medulla niche supporting germinal center response in myasthenia gravis-associated thymoma
Yasumizu Y, Kinoshita M, Zhang M, Motooka D, Suzuki K, Nojima S, Koizumi N, Okuzaki D, Funaki S, Shintani Y, Ohkura N, Morii E, Okuno T, Mochizuki H. Spatial transcriptomics elucidates medulla niche supporting germinal center response in myasthenia gravis-associated thymoma. Cell Reports 2024, 43: 114677. PMID: 39180749, DOI: 10.1016/j.celrep.2024.114677.Peer-Reviewed Original ResearchMyasthenia gravisMedullary thymic epithelial cellsGerminal center responseRegulatory T cellsImmune cell compositionMigratory dendritic cellsThymic epithelial cellsCortico-medullary junctionImmune microenvironmentDendritic cellsT cellsChemokine patternsThymus abnormalitiesHyperplasia samplesThymomaSpatial transcriptomic analysisEpithelial cellsMG pathologyMedullary regionCenter responseMedullaCell compositionCortical regionsPathologyCells
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 phaseInfection
2022
CCR8-targeted specific depletion of clonally expanded Treg cells in tumor tissues evokes potent tumor immunity with long-lasting memory
Kidani Y, Nogami W, Yasumizu Y, Kawashima A, Tanaka A, Sonoda Y, Tona Y, Nashiki K, Matsumoto R, Hagiwara M, Osaki M, Dohi K, Kanazawa T, Ueyama A, Yoshikawa M, Yoshida T, Matsumoto M, Hojo K, Shinonome S, Yoshida H, Hirata M, Haruna M, Nakamura Y, Motooka D, Okuzaki D, Sugiyama Y, Kinoshita M, Okuno T, Kato T, Hatano K, Uemura M, Imamura R, Yokoi K, Tanemura A, Shintani Y, Kimura T, Nonomura N, Wada H, Mori M, Doki Y, Ohkura N, Sakaguchi S. CCR8-targeted specific depletion of clonally expanded Treg cells in tumor tissues evokes potent tumor immunity with long-lasting memory. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2114282119. PMID: 35140181, PMCID: PMC8851483, DOI: 10.1073/pnas.2114282119.Peer-Reviewed Original ResearchConceptsTumor TregsTumor immunityMAb treatmentTumor tissuesT cellsLong-lasting memoryCD4<sup>+</sup> regulatory T cellsPD-1 immune checkpoint blockadeCures of established tumorsInduce severe autoimmune diseaseSuppress antitumor immune responsesImmune responseT cell receptor clonotypesImmune checkpoint blockadeSystemic Treg depletionAntitumor immune responseConventional T cellsRegulatory T cellsTumor-associated antigensChemokine receptor CCR8Several autoimmune diseasesSecondary immune responseTreg depletionCheckpoint blockadePD-1
2021
Reply to Slominski et al.: UVB irradiation induces proenkephalin+ regulatory T cells with a wound-healing function
Shime H, Odanaka M, Tsuiji M, Matoba T, Imai M, Yasumizu Y, Uraki R, Minohara K, Watanabe M, Bonito A, Fukuyama H, Ohkura N, Sakaguchi S, Morita A, Yamazaki S. Reply to Slominski et al.: UVB irradiation induces proenkephalin+ regulatory T cells with a wound-healing function. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2021919118. PMID: 33414270, PMCID: PMC7826361, DOI: 10.1073/pnas.2021919118.Peer-Reviewed Original Research
2020
Proenkephalin+ regulatory T cells expanded by ultraviolet B exposure maintain skin homeostasis with a healing function
Shime H, Odanaka M, Tsuiji M, Matoba T, Imai M, Yasumizu Y, Uraki R, Minohara K, Watanabe M, Bonito A, Fukuyama H, Ohkura N, Sakaguchi S, Morita A, Yamazaki S. Proenkephalin+ regulatory T cells expanded by ultraviolet B exposure maintain skin homeostasis with a healing function. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 20696-20705. PMID: 32769209, PMCID: PMC7456133, DOI: 10.1073/pnas.2000372117.Peer-Reviewed Original ResearchConceptsTreg cellsUltraviolet B exposureUnique TCR repertoireFoxp3 transcription factorRegulatory T cellsSkin homeostasisSkin explant assayImmunological self-toleranceFunctional regulatory TUltraviolet BWound healingSuppress various immune responsesEndogenous opioid precursorsSkin TregsExpressed CD25Regulatory TTCR repertoireProenkephalin expressionT cellsSelf-toleranceWound closure assayImmune responseTregsInflammatory responseMet-Enk