Developmental and cellular age direct conversion of CD4+ T cells into ROR?+ or Helios+ colon Treg cells.

ABSTRACT: ROR?+ 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 ROR?+ 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 ROR?-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 ROR?+ 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.

SUBMITTER: Pratama A 

PROVIDER: S-EPMC7037252 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature