Heterogeneity and clonality of kidney-infiltrating T cells in murine lupus nephritis.
Heterogeneity and clonality of kidney-infiltrating T cells in murine lupus nephritis.
复制标题
狼疮性肾炎小鼠肾脏浸润性T细胞的异质性和克隆性
DOI：
10.1172/jci.insight.156048
复制
发表时间：
2022-04-22
期刊：
影响因子：
8
通讯作者：
Tilstra, Jeremy S.
中科院分区：
文献类型：
--
作者：
Smita, Shuchi;Chikina, Maria;Shlomchik, Mark J.;Tilstra, Jeremy S.
我们之前发现小鼠狼疮性肾炎（LN）中的肾浸润T细胞（kit）类似于浸润肿瘤的功能失调T细胞。这一意想不到的发现提出了一个问题，即如何调和试剂盒的“耗尽”表型与LN中持续的组织破坏。为了解决这个问题，我们在小鼠狼疮模型中进行了kit的单细胞RNA-Seq和TCR-Seq。我们发现CD8+ kit首先存在于过渡状态，然后在克隆扩展和进化到耗尽。另一方面，CD4+试剂盒不适合当前的分化模式，但包括缺氧和细胞毒性亚群，具有普遍的衰竭特征。因此，自身免疫性肾炎不同于急性病原体免疫；相反，肾脏微环境通过逐步诱导衰竭状态来抑制T细胞。我们的研究结果表明，LN是一种慢性疾病，是由功能失调的T细胞及其前体在衰竭过程中引起的损伤缓慢演变的结果。这些发现对自身免疫和肿瘤免疫学都有意义。
We previously found that kidney-infiltrating T cells (KITs) in murine lupus nephritis (LN) resembled dysfunctional T cells that infiltrate tumors. This unexpected finding raised the question of how to reconcile the “exhausted” phenotype of KITs with ongoing tissue destruction in LN. To address this, we performed single-cell RNA-Seq and TCR-Seq of KITs in murine lupus models. We found that CD8+ KITs existed first in a transitional state, before clonally expanding and evolving toward exhaustion. On the other hand, CD4+ KITs did not fit into current differentiation paradigms but included both hypoxic and cytotoxic subsets with a pervasive exhaustion signature. Thus, autoimmune nephritis is unlike acute pathogen immunity; rather, the kidney microenvironment suppresses T cells by progressively inducing exhausted states. Our findings suggest that LN, a chronic condition, results from slow evolution of damage caused by dysfunctional T cells and their precursors on the way to exhaustion. These findings have implications for both autoimmunity and tumor immunology.
登录
查看更多内容
影响因子：
3.3
作者：
Clark MR;Trotter K;Chang A
通讯作者：
Chang A
影响因子：
16.6
作者：
Ahrends, Tomasz;Busselaar, Julia;Borst, Jannie
通讯作者：
Borst, Jannie
影响因子：
16.6
作者：
Lanata, Cristina M.;Paranjpe, Ishan;Criswell, Lindsey A.
通讯作者：
Criswell, Lindsey A.
影响因子：
30.5
作者：
Arazi, Arnon;Rao, Deepak A.;Goldman, Daniel H.
通讯作者：
Goldman, Daniel H.
影响因子：
17.1
作者：
Chen PM;Wilson PC;Shyer JA;Veselits M;Steach HR;Cui C;Moeckel G;Clark MR;Craft J
通讯作者：
Craft J