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Single-cell RNA-sequencing identifies the developmental trajectory of C-Myc-dependent NK1.1- T-bet+ intraepithelial lymphocyte precursors.

Abstract：

:Natural intraepithelial lymphocytes (IELs) are thymus-derived adaptive immune cells, which are important contributors to intestinal immune homeostasis. Similar to other innate-like T cells, they are induced in the thymus through high-avidity interaction that would otherwise lead to clonal deletion in conventional CD4 and CD8 T cells. By applying single-cell RNA-sequencing (scRNA-seq) on a heterogeneous population of thymic CD4-CD8αβ-TCRαβ+NK1.1- IEL precursors (NK1.1- IELPs), we define a developmental trajectory that can be tracked based on the sequential expression of CD122 and T-bet. Moreover, we identify the Id proteins Id2 and Id3 as a novel regulator of IELP development and show that all NK1.1- IELPs progress through a PD-1 stage that precedes the induction of T-bet. The transition from PD-1 to T-bet is regulated by the transcription factor C-Myc, which has far reaching effects on cell cycle, energy metabolism, and the translational machinery during IELP development. In summary, our results provide a high-resolution molecular framework for thymic IEL development of NK1.1- IELPs and deepen our understanding of this still elusive cell type.

journal_name

Mucosal Immunol

journal_title

Mucosal immunology

authors

Hummel JF,Zeis P,Ebert K,Fixemer J,Konrad P,Schachtrup C,Arnold SJ,Grün D,Tanriver Y

doi

10.1038/s41385-019-0220-y

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

257-270

issue

2

eissn

1933-0219

issn

1935-3456

pii

10.1038/s41385-019-0220-y

journal_volume

13

pub_type

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