AUTHOR=Chen Yichen , Zhu Jue , Chen Liang , Shen Yuanyuan , Zhang Jing , Wang Qiming 

TITLE=SFRP4+IGFBP5hi NKT cells induced neural-like cell differentiation to contribute to adenomyosis pain

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.945504

DOI=10.3389/fimmu.2022.945504

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Method</title><p>This study analyzed the tissue-cell samples from adenomyosis with or without pain by single-cell sequencing.</p></sec><sec><title>Result</title><p>We found a specific population of secreted frizzled-related protein 4 (SFRP4)<sup>+</sup>NKT cells and a large amount of undifferentiated multipotent stem cells in the adenomyosis pain group. We discovered that a high expression of <italic>IGFBP5</italic> in SFRP4<sup>+</sup>NKT cells could promote the differentiation of multipotent stem cells into neural-like cells <italic>via</italic> the single-cell trajectory. Through verification by the sample, we found that the degree of the expression of the neuronal marker <italic>NEFM</italic> was correlated with the duration of pain in adenomyosis patients. The expression of IGFBP5 was positively correlated with the pain scores of adenomyosis patients.</p></sec><sec><title>Conclusion</title><p>Collectively, these findings suggest that SFRP4<sup>+</sup>IGFBP5<sup>hi</sup> NKT cells were capable of converting part of the stem cells into neurogenic cells and inducing adenomyosis pain.</p></sec>