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Publication : Developmental and cellular age direct conversion of CD4+ T cells into RORγ+ or Helios+ colon Treg cells.

First Author  Pratama A Year  2020
Journal  J Exp Med Volume  217
Issue  1 PubMed ID  31685531
Mgi Jnum  J:336878 Mgi Id  MGI:6392639
Doi  10.1084/jem.20190428 Citation  Pratama A, et al. (2020) Developmental and cellular age direct conversion of CD4+ T cells into RORgamma+ or Helios+ colon Treg cells. J Exp Med 217(1)
abstractText  RORgamma+ and Helios+ Treg cells in the colon are phenotypically and functionally distinct, but their origins and relationships are poorly understood. In monocolonized and normal mice, single-cell RNA-seq revealed sharing of TCR clonotypes between these Treg cell populations, potentially denoting a common progenitor. In a polyclonal Treg cell replacement system, naive conventional CD4+ (Tconv) cells, but not pre-existing tTregs, could differentiate into RORgamma+ pTregs upon interaction with gut microbiota. A smaller proportion of Tconv cells converted into Helios+ pTreg cells, but these dominated when the Tconv cells originated from preweaning mice. T cells from infant mice were predominantly immature, insensitive to RORgamma-inducing bacterial cues and to IL6, and showed evidence of higher TCR-transmitted signals, which are also characteristics of recent thymic emigrants (RTEs). Correspondingly, transfer of adult RTEs or Nur77high Tconv cells mainly yielded Helios+ pTreg cells, recapitulating the infant/adult difference. Thus, CD4+ Tconv cells can differentiate into both RORgamma+ and Helios+ pTreg cells, providing a physiological adaptation of colonic Treg cells as a function of the age of the cell or of the individual.
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