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TGF-β介导的SATB1沉默促进Tfh细胞分化和肿瘤内三级淋巴结构的形成
作者:小柯机器人 发布时间:2022/1/16 13:12:25

美国李-莫菲特癌症研究中心Jose R. Conejo-Garcia课题组发现,TGF-β介导的SATB1沉默促进Tfh细胞分化和肿瘤内三级淋巴结构的形成 。相关论文于2022年1月11日发表在《免疫》杂志上。

研究人员检查了基因组组织者SATB1调节PD-1表达对T滤泡辅助(Tfh)细胞分化的影响。对CD4CreSatb1f/f小鼠进行疫苗接种可富集抗原特异性Tfh细胞,并且TGF-β介导的SATB1 抑制增强了人类T细胞的Tfh分化。从机制上讲,Satb1-/-CD4+ T细胞中的高Icos表达通过阻止T滤泡调节细胞倾斜来促进Tfh细胞分化,并导致体内同种型转换B细胞反应增加。 CD4CreSatb1f/f小鼠的卵巢肿瘤积累了肿瘤抗原特异性、LIGHT+CXCL13+IL-21+ Tfh细胞和三级淋巴结构 (TLS)。TLS形成以CD4+ T 细胞和CXCL13依赖性方式降低了肿瘤生长。 Tfh细胞而不是初始CD4+ T 细胞的转移在肿瘤灶诱导TLS并减少肿瘤生长。因此,TGF-β介导的Satb1沉默能够促进Tfh细胞分化,从而深入了解肿瘤内TLS的发生。

据了解,Tfh细胞上的免疫检查点受体PD-1促进Tfh:B细胞相互作用和组织内的适当定位。

附:英文原文

Title: TGF-β-mediated silencing of genomic organizer SATB1 promotes Tfh cell differentiation and formation of intra-tumoral tertiary lymphoid structures

Author: Ricardo A. Chaurio, Carmen M. Anadon, Tara Lee Costich, Kyle K. Payne, Subir Biswas, Carly M. Harro, Carlos Moran, Antonio C. Ortiz, Carla Cortina, Kristen E. Rigolizzo, Kimberly B. Sprenger, Jessica A. Mine, Patrick Innamarato, Gunjan Mandal, John J. Powers, Alexandra Martin, Zhitao Wang, Sumit Mehta, Bradford A. Perez, Roger Li, John Robinson, Jodi L. Kroeger, Tyler J. Curiel, Xiaoqing Yu, Paulo C. Rodriguez, Jose R. Conejo-Garcia

Issue&Volume: 2022/01/11

Abstract: The immune checkpoint receptor PD-1 on T follicular helper (Tfh) cells promotes Tfh:B cell interactions and appropriate positioning within tissues. Here, we examined the impact of regulation of PD-1 expression by the genomic organizer SATB1 on Tfh cell differentiation. Vaccination of CD4CreSatb1f/f mice enriched for antigen-specific Tfh cells, and TGF-β-mediated repression of SATB1 enhanced Tfh differentiation of human T cells. Mechanistically, high Icos expression in Satb1/ CD4+ T cells promoted Tfh cell differentiation by preventing T follicular regulatory cell skewing and resulted in increased isotype-switched B cell responses in vivo. Ovarian tumors in CD4CreSatb1f/f mice accumulated tumor antigen-specific, LIGHT+CXCL13+IL-21+ Tfh cells and tertiary lymphoid structures (TLS). TLS formation decreased tumor growth in a CD4+ T cell and CXCL13-dependent manner. The transfer of Tfh cells, but not naive CD4+ T cells, induced TLS at tumor beds and decreased tumor growth. Thus, TGF-β-mediated silencing of Satb1 licenses Tfh cell differentiation, providing insight into the genesis of TLS within tumors.

DOI: 10.1016/j.immuni.2021.12.007

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00543-4

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx