
만성 항원 자극은 체내에서 IL-10을 생산하는 T 조절 1형 세포의 형성을 유발할 수 있다. T 세포 여포 도움 세포가 T 조절 1형 세포의 전구체이며, T 세포 여포 도움 세포에서 T 조절 1형 세포로의 전환 과정은 상반된 전사인자 유전자 발현 프로그램의 점진적 손실과 획득을 통해 진행된다.


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Chronic antigenic stimulation can trigger the formation of IL-10-producing T-regulatory type 1 (TR1) cells in vivo . We have recently shown that T follicular helper (TFH) cells are precursors of TR1 cells and that the TFH-to-TR1 cell transdifferentiation process is characterized by the progressive loss and acquisition of opposing transcription factor gene expression programs that evolve through at least one transitional cell stage. Here, we use a broad range of bulk and single-cell transcriptional and epigenetic tools to investigate the epigenetic underpinnings of this process. At the single cell level, the TFH-to-TR1 cell transition is accompanied by both, downregulation of TFH cell-specific gene expression due to loss of chromatin accessibility, and upregulation of TR1 cell-specific genes linked to chromatin regions that remain accessible throughout the transdifferentiation process, with minimal generation of new open chromatin regions. By interrogating the epigenetic status of accessible TR1 genes on purified TFH and conventional T cells, we find that most of these genes, including Il10 , are already poised for expression at the TFH cell stage. Whereas these genes are closed and hypermethylated in Tconv cells, they are accessible, hypomethylated and enriched for H3K27ac-marked and hypomethylated active enhancers in TFH cells. These enhancers are enriched for binding sites for the TFH and TR1-associated transcription factors TOX-2, IRF4 and c-MAF. Together, these data suggest that the TR1 gene expression program is genetically imprinted at the TFH cell stage.

### Competing Interest Statement

P. Santamaria is founder, scientific officer and stockholder of Parvus Therapeutics. He is inventor on patents on pMHC-based nanomedicines and receives funding from the company. He also has a consulting agreement with Sanofi. The other authors declare no competing interests.

T-follicular helper cells are epigenetically poised to transdifferentiate into T-regulatory type-1 cells

t-세포-여포-도움-세포는-t-조절-1형-세포로-전환될-수-있도록-후성유전학적으로-준비되어-있다


T 세포 여포 도움 세포는 T 조절 1형 세포로 전환될 수 있도록 후성유전학적으로 준비되어 있다
