SFRP4/IGFBP5-NKT 细胞诱导神经样细胞分化有助于腺肌病疼痛。

SFRP4IGFBP5 NKT cells induced neural-like cell differentiation to contribute to adenomyosis pain.

机构信息

Department of Gynaecology, Ningbo Women & Children's Hospital, Ningbo University, Ningbo, China.

出版信息

Front Immunol. 2022 Nov 30;13:945504. doi: 10.3389/fimmu.2022.945504. eCollection 2022.

Abstract

BACKGROUND

Adenomyosis is an estrogen-dependent gynecological disease. The pathogenesis of chronic pain, the main clinical symptom of adenomyosis, remains undefined. As a combination lymphocyte with both T-cell and natural killer (NK)-cell properties, NK T (NKT) cells play a role in immune defense against numerous diseases and modulate cell differentiation.

METHOD

This study analyzed the tissue-cell samples from adenomyosis with or without pain by single-cell sequencing.

RESULT

We found a specific population of secreted frizzled-related protein 4 (SFRP4)NKT cells and a large amount of undifferentiated multipotent stem cells in the adenomyosis pain group. We discovered that a high expression of in SFRP4NKT cells could promote the differentiation of multipotent stem cells into neural-like cells the single-cell trajectory. Through verification by the sample, we found that the degree of the expression of the neuronal marker was correlated with the duration of pain in adenomyosis patients. The expression of IGFBP5 was positively correlated with the pain scores of adenomyosis patients.

CONCLUSION

Collectively, these findings suggest that SFRP4IGFBP5 NKT cells were capable of converting part of the stem cells into neurogenic cells and inducing adenomyosis pain.

摘要

背景

子宫腺肌病是一种雌激素依赖性妇科疾病。其主要临床症状慢性疼痛的发病机制尚不清楚。自然杀伤 T(NKT)细胞作为兼具 T 细胞和自然杀伤(NK)细胞特性的组合淋巴细胞,在多种疾病的免疫防御中发挥作用,并调节细胞分化。

方法

本研究通过单细胞测序分析了伴或不伴疼痛的子宫腺肌病的组织细胞样本。

结果

我们在有疼痛症状的子宫腺肌病组中发现了一个分泌卷曲相关蛋白 4(SFRP4)NKT 细胞的特定群体和大量未分化的多能干细胞。我们发现 SFRP4NKT 细胞中高表达可以促进多能干细胞向神经样细胞分化——单细胞轨迹。通过样本验证,我们发现神经元标记物的表达程度与子宫腺肌病患者疼痛持续时间相关。IGFBP5 的表达与子宫腺肌病患者的疼痛评分呈正相关。

结论

综上所述,这些发现表明 SFRP4IGFBP5 NKT 细胞能够将部分干细胞转化为神经原性细胞,并诱导子宫腺肌病疼痛。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ad5/9750790/3ceabc76dbc6/fimmu-13-945504-g001.jpg

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