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CD161+ Tconv and Treg share transcriptome and display a migratory phenotype which is modified at the inflamed site

ABSTRACT: Regulatory T cells (Treg) are a cornerstone of immune regulation. Recent evidence indicates that human Treg show plasticity in specific settings. A subpopulation of Treg expressing CD161, a marker associated with T helper (Th)17 cells, have T effector -like characteristics and are enriched at sites of autoimmune inflammation. Here we used RNAseq to confirm the effector-like signature of CD161+ Treg and demonstrated a shared transcriptional signature between CD161+ Treg and CD161+ conventional T cells (Tconv). Pathway analysis suggested that CD161+ T cells have a migratory phenotype, expressing high levels of CCR9 and integrin α4β7, markers associated with gut homing. In response to all-trans retinoic acid, CD161+ T cells expressed higher levels of CCR9 and integrin α4β7 than CD161- T cells. Our data suggest that blood CD161+ T cells may have adopted gut homing properties upon retinoic acid exposure. In contrast to their peripheral counterparts, CD161+ T cells from the site of autoimmune arthritis have a diminished gut homing phenotype and blunted response to retinoic acid. In health, the TCRβ repertoires of CD161+ and CD161- T cells showed limited overlap whereas there is clear overlap in T cell clones from synovial fluid of autoimmune arthritis patients. We therefore propose that CD161+ and CD161- T cells are largely distinct populations in the healthy immune system but that the inflamed site creates an environment where CD161 levels in T cells can be altered, potentially contributing to disease pathogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE86452 | GEO | 2017/03/27

SECONDARY ACCESSION(S): PRJNA341951

REPOSITORIES: GEO

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