Fewer LAG-3(+) T Cells in Relapsing-Remitting Multiple Sclerosis and Type 1 Diabetes.
Fewer LAG-3(+) T Cells in Relapsing-Remitting Multiple Sclerosis and Type 1 Diabetes.
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DOI：
10.4049/jimmunol.2100850
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发表时间：
2022-02-01
期刊：
影响因子：
--
通讯作者：
Buckner JH
中科院分区：
文献类型：
--
作者：
Jones BE;Maerz MD;Bahnson HT;Somasundaram A;McCarthy LH;Speake C;Buckner JH
共抑制受体淋巴细胞活化基因3（LAG-3）是负调节T细胞活化、增殖和稳态的免疫检查点分子。在自身免疫易感背景或诱导性疾病模型中，LAG-3的阻断或缺失已被证明会加重疾病。我们观察到复发缓解型多发性硬化症（RRMS）和1型糖尿病受试者的LAG-3+ CD 4和CD 8 T细胞显著减少。低LAG-3蛋白表达与mRNA表达的改变有关，而与细胞表面裂解无关。抑制LAG-3的功能研究表明，在RRMS受试者中，LAG-3保留了其抑制T细胞增殖的能力。然而，LAG-3表达与细胞凋亡标志物的表达相关，表明低LAG-3在T细胞抵抗细胞死亡中的作用。在来自RRMS受试者的T细胞中，我们观察到LAG-3表达的整体失调，其源于转录降低并在T细胞刺激后持续存在。这些发现进一步支持LAG-3激动剂在治疗人自身免疫中的潜在临床益处。
The co-inhibitory receptor lymphocyte activation gene 3 (LAG-3) is an immune checkpoint molecule that negatively regulates T cell activation, proliferation, and homeostasis. Blockade or deletion of LAG-3 in autoimmune-prone backgrounds or induced-disease models has been shown to exacerbate disease. We observed significantly fewer LAG-3+ CD4 and CD8 T cells from subjects with relapsing-remitting multiple sclerosis (RRMS) and type 1 diabetes. Low LAG-3 protein expression was linked to alterations in mRNA expression and not cell surface cleavage. Functional studies inhibiting LAG-3 suggest that in RRMS subjects, LAG-3 retains its ability to suppress T cell proliferation. However, LAG-3 expression was associated with the expression of markers of apoptosis indicating a role for low LAG-3 in T cell resistance to cell death. In T cells from RRMS subjects, we observed a global dysregulation of LAG-3 expression stemming from decreased transcription and persisting after T cell stimulation. These findings further support the potential clinical benefits of a LAG-3 agonist in the treatment of human autoimmunity.
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影响因子：
--
作者：
Joller N;Kuchroo VK
通讯作者：
Kuchroo VK
影响因子：
24.8
作者：
Andrews LP;Somasundaram A;Moskovitz JM;Szymczak-Workman AL;Liu C;Cillo AR;Lin H;Normolle DP;Moynihan KD;Taniuchi I;Irvine DJ;Kirkwood JM;Lipson EJ;Ferris RL;Bruno TC;Workman CJ;Vignali DAA
通讯作者：
Vignali DAA
DOI：
10.1084/jem.20060210
发表时间：
2006-06-12
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Koguchi K;Anderson DE;Yang L;O'Connor KC;Kuchroo VK;Hafler DA
通讯作者：
Hafler DA
影响因子：
3.4
作者：
Garcia, Catherine R.;Jayswal, Rani;Villano, John L.
通讯作者：
Villano, John L.
影响因子：
9.9
作者：
Comi, C;Leone, M;Dianzani, U
通讯作者：
Dianzani, U