首页|A T follicular helper cell origin for T regulatory type 1 cells

A T follicular helper cell origin for T regulatory type 1 cells

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Chronic antigenic stimulation can trigger the differentiation of antigen-experienced CD4+T cells into T regulatory type 1(TR1)cells,a subset of interleukin-10-producing Treg cells that do not express FOXP3.The identities of the progenitor(s)and transcriptional regulators of this T-cell subset remain unclear.Here,we show that the peptide-major histocompatibility complex class II(pMHCII)monospecific immunoregulatory T-cell pools that arise in vivo in different genetic backgrounds in response to pMHCII-coated nanoparticles(pMHCII-NPs)are invariably comprised of oligoclonal subpools of T follicular helper(TFH)and TR1 cells with a nearly identical clonotypic composition but different functional properties and transcription factor expression profiles.Pseudotime analyses of scRNAseq data and multidimensional mass cytometry revealed progressive downregulation and upregulation of TFH and TR1 markers,respectively.Furthermore,pMHCII-NPs trigger cognate TR1 cell formation in TFH cell-transfused immunodeficient hosts,and T-cell-specific deletion of Bcl6 or Irf4 blunts both the TFH expansion and TR1 formation induced by pMHCII-NPs.In contrast,deletion of Prdm1 selectively abrogates the TFH-to-TR1 conversion.Bcl6 and Prdm1 are also necessary for anti-CD3 mAb-induced TR1 formation.Thus,TFH cells can differentiate into TR1 cells in vivo,and BLIMP1 is a gatekeeper of this cellular reprogramming event.

T-regulatory type 1(TR1)cellsautoimmunityT follicular helper(TFH)cellstransdifferentiationnanomedicine

Patricia Solé、Jun Yamanouchi、Josep Garnica、Muhammad Myn Uddin、Robert Clarke、Joel Moro、Nahir Garabatos、Shari Thiessen、Mireia Ortega、Santiswarup Singha、Debajyoti Mondal、César Fandos、Julio Saez-Rodriguez、Yang Yang、Pau Serra、Pere Santamaria

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Institut D'Investigacions Biomèdiques August Pi i Sunyer,Barcelona,Spain

Department of Microbiology,Immunology and Infectious Diseases,Snyder Institute for Chronic Diseases,Cumming School of Medicine,University of Calgary,Calgary,AB,Canada

Institute of Computational Biomedicine,Faculty of Medicine,Heidelberg University,Heidelberg,Germany

Department of Biochemistry and Molecular Biology,Cumming School of Medicine,University of Calgary,Calgary,AB,Canada

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Canadian Institutes of Health Research(CIHR)Canadian Institutes of Health Research(CIHR)Canadian Institutes of Health Research(CIHR)Canadian Institutes of Health Research(CIHR)Canadian Institutes of Health Research(CIHR)Genome Canada(GAPP program)Praespero Foundation,the Alberta Diabetes FoundationISCIIIFEDERFEDERMinisterio de Ciencia e Innovación of SpainMinisterio de Ciencia e Innovación of SpainGeneralitat de Catalunya(SGR and CERCA Programmes)Red Espa?ola de Supercomputación(RES,providing CSUC resources)a JDRF Career Development Awardpredoctoral studentships from FPU(MCIN)

FDN-353029PJT-479040PJT-479038FRN-168480DT4-179512PIE14/00027PI15/0797MCINPID2021-125493OB-I00

2023

10.1038/s41423-023-00989-z

中国免疫学杂志(英文版)
中国免疫学会

中国免疫学杂志(英文版)

CSTPCDCSCDSCI
影响因子：0.731
ISSN：1672-7681
年,卷(期)：2023.20(5)
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