The MS4A gene family encodes 18 tetraspanin-like proteins, most of which with unknown function. MS4A1 (CD20), MS4A2 (FcεRIβ), MS4A3 (HTm4), and MS4A4A play important roles in immunity, whereas expression and function of other members of the family are unknown. The present investigation was designed to obtain an expression fingerprint of MS4A family members, using bioinformatics analysis of public databases, RT-PCR, and protein analysis when possible. MS4A3, MS4A4A, MS4A4E, MS4A6A, MS4A7, and MS4A14 were expressed by myeloid cells. MS4A6A and MS4A14 were expressed in circulating monocytes and decreased during monocyte-to-Mϕ differentiation in parallel with an increase in MS4A4A expression. Analysis of gene expression regulation revealed a strong induction of MS4A4A, MS4A6A, MS4A7, and MS4A4E by glucocorticoid hormones. Consistently with in vitro findings, MS4A4A and MS4A7 were expressed in tissue Mϕs from COVID-19 and rheumatoid arthritis patients. Interestingly, MS4A3, selectively expressed in myeloid precursors, was found to be a marker of immature circulating neutrophils, a cellular population associated to COVID-19 severe disease. The results reported here show that members of the MS4A family are differentially expressed and regulated during myelomonocytic differentiation, and call for assessment of their functional role and value as therapeutic targets.

中文翻译：

---

MS4A家族成员在生理病理条件下骨髓细胞中的差异表达与调控

MS4A 基因家族编码 18 种四跨膜蛋白样蛋白，其中大部分功能未知。MS4A1 (CD20)、MS4A2 (FcεRIβ)、MS4A3 (HTm4) 和 MS4A4A 在免疫中起重要作用，而该家族其他成员的表达和功能未知。本研究旨在获取 MS4A 家族成员的表达指纹，尽可能使用公共数据库的生物信息学分析、RT-PCR 和蛋白质分析。MS4A3、MS4A4A、MS4A4E、MS4A6A、MS4A7 和 MS4A14 由骨髓细胞表达。MS4A6A 和 MS4A14 在循环单核细胞中表达，并在单核细胞向 Mφ 分化过程中减少，同时 MS4A4A 表达增加。基因表达调控分析显示糖皮质激素强烈诱导 MS4A4A、MS4A6A、MS4A7 和 MS4A4E。与体外研究结果一致，MS4A4A 和 MS4A7 在 COVID-19 和类风湿性关节炎患者的组织 Mφs 中表达。有趣的是，在骨髓前体中选择性表达的 MS4A3 被发现是未成熟循环中性粒细胞的标志物，这是一种与 COVID-19 严重疾病相关的细胞群。这里报道的结果表明，MS4A 家族的成员在骨髓单核细胞分化过程中存在差异表达和调节，因此需要评估它们作为治疗靶点的功能作用和价值。