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前沿：Toll样受体1（TLR1）的基因变异与Pam3CSK4诱导的效应T细胞对调节性T细胞抑制的抗性相关。

Cutting edge: Genetic variation in TLR1 is associated with Pam3CSK4-induced effector T cell resistance to regulatory T cell suppression.

作者信息

Mikacenic Carmen, Schneider Anya, Radella Frank, Buckner Jane H, Wurfel Mark M

机构信息

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington, Seattle, WA 98104; and

Translational Research Program, Benaroya Research Institute, Seattle, WA 98101.

出版信息

J Immunol. 2014 Dec 15;193(12):5786-90. doi: 10.4049/jimmunol.1401185. Epub 2014 Nov 5.

DOI:10.4049/jimmunol.1401185
PMID:25378593
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4258445/
Abstract

TLR play essential roles in the initiation and modulation of immune responses. TLR1/TLR2 heterodimers recognize triacylated bacterial lipopeptides, including the synthetic TLR1/2 lipopeptide Pam3CSK4. Genetic variation in TLR1 is associated with outcomes in diseases in which regulatory T cells (Treg) play a role, including asthma and allergy. To determine whether genetic polymorphisms in TLR1 are associated with alterations in Treg suppression of effector T cells (Teff), we performed in vitro suppression assays in healthy individuals with various haplotypes in TLR1. We show that functional genetic polymorphisms in TLR1 modify surface expression of TLR1 on T lymphocytes and confer enhanced Teff resistance to Treg suppression in the presence of Pam3CSK4. These effects are mediated, in part, by IL-6 and inhibited by blocking IL-6 signaling through STAT3. These findings suggest that TLR1 polymorphisms could influence immune-related disease through Teff resistance to Treg suppression.

摘要

Toll样受体（TLR）在免疫反应的启动和调节中发挥着重要作用。TLR1/TLR2异二聚体可识别三酰化细菌脂肽，包括合成的TLR1/2脂肽Pam3CSK4。TLR1的基因变异与调节性T细胞（Treg）发挥作用的疾病（包括哮喘和过敏）的预后相关。为了确定TLR1基因多态性是否与Treg对效应T细胞（Teff）抑制作用的改变相关，我们对具有TLR1不同单倍型的健康个体进行了体外抑制试验。我们发现，TLR1的功能性基因多态性可改变T淋巴细胞表面TLR1的表达，并在Pam3CSK4存在的情况下使Teff对Treg抑制作用的抗性增强。这些效应部分由白细胞介素-6（IL-6）介导，并通过信号转导和转录激活因子3（STAT3）阻断IL-6信号传导而受到抑制。这些发现表明，TLR1多态性可能通过Teff对Treg抑制作用的抗性影响免疫相关疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8538/4258445/1910ae049631/nihms637754f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8538/4258445/94056f3c79b6/nihms637754f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8538/4258445/a6755a76ef07/nihms637754f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8538/4258445/fcd7ac711653/nihms637754f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8538/4258445/1910ae049631/nihms637754f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8538/4258445/94056f3c79b6/nihms637754f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8538/4258445/a6755a76ef07/nihms637754f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8538/4258445/fcd7ac711653/nihms637754f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8538/4258445/1910ae049631/nihms637754f4.jpg

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