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催乳素增加狼疮易感 MRL/lpr 小鼠滤泡辅助性 T 细胞的频率,增强其 IL21 分泌和 OX40 表达。

Prolactin Increases the Frequency of Follicular T Helper Cells with Enhanced IL21 Secretion and OX40 Expression in Lupus-Prone MRL/lpr Mice.

机构信息

UIM en Inmunología, Hospital de Pediatría, CMN Siglo XXI, Instituto Mexicano del Seguro Social, Mexico.

Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México "Federico Gómez", Mexico.

出版信息

J Immunol Res. 2021 Mar 8;2021:6630715. doi: 10.1155/2021/6630715. eCollection 2021.

DOI:10.1155/2021/6630715
PMID:33763492
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7963914/
Abstract

Systemic lupus erythematosus is characterized by high levels of IgG class autoantibodies that contribute to the pathophysiology of the disease. The formation of these autoantibodies occurs in the germinal centers, where there is cooperation between follicular T helper cells (T) and autoreactive B cells. Prolactin has been reported to exacerbate the clinical manifestations of lupus by increasing autoantibody concentrations. The objective of this study was to characterize the participation of prolactin in the differentiation and activation of T cells, by performing in vivo and in vitro tests with lupus-prone mice, using flow cytometry and real-time PCR. We found that T cells express the long isoform of the prolactin receptor and promoted STAT3 phosphorylation. Receptor expression was higher in MRL/lpr mice and correlative with the manifestations of the disease. Although prolactin does not intervene in the differentiation of T cells, it does favor their activation by increasing the percentage of T OX40 and T IL21 cells, as well as leading to high serum concentrations of IL21. These results support a mechanism in which prolactin participates in the emergence of lupus by inducing overactive T cells and perhaps promoting dysfunctional germinal centers.

摘要

系统性红斑狼疮的特征是 IgG 类自身抗体水平升高,这些抗体导致疾病的病理生理变化。这些自身抗体的形成发生在生发中心,滤泡辅助性 T 细胞(T 细胞)和自身反应性 B 细胞之间存在合作。催乳素被报道通过增加自身抗体浓度来加重狼疮的临床表现。本研究的目的是通过使用狼疮易感小鼠进行体内和体外试验,使用流式细胞术和实时 PCR 来描述催乳素在 T 细胞分化和激活中的参与。我们发现 T 细胞表达催乳素受体的长型同工型,并促进 STAT3 磷酸化。受体表达在 MRL/lpr 小鼠中更高,并与疾病的表现相关。虽然催乳素不干预 T 细胞的分化,但它通过增加 T OX40 和 T IL21 细胞的百分比,以及导致高水平的血清 IL21,有利于 T 细胞的激活。这些结果支持一种机制,即催乳素通过诱导过度活跃的 T 细胞并可能促进功能失调的生发中心参与狼疮的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd66/7963914/a783205f776e/JIR2021-6630715.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd66/7963914/b4b485c0fea9/JIR2021-6630715.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd66/7963914/3217aed10b62/JIR2021-6630715.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd66/7963914/53703af752e2/JIR2021-6630715.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd66/7963914/77ad878e3b8d/JIR2021-6630715.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd66/7963914/187dcdd0490f/JIR2021-6630715.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd66/7963914/a783205f776e/JIR2021-6630715.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd66/7963914/b4b485c0fea9/JIR2021-6630715.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd66/7963914/3217aed10b62/JIR2021-6630715.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd66/7963914/53703af752e2/JIR2021-6630715.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd66/7963914/77ad878e3b8d/JIR2021-6630715.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd66/7963914/187dcdd0490f/JIR2021-6630715.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd66/7963914/a783205f776e/JIR2021-6630715.006.jpg

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