Department of Otorhinolaryngology-Head and Neck Surgery, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon 24252, Republic of Korea.
Institute of New Frontier Research, Division of Big Data and Artificial Intelligence, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon 24252, Republic of Korea.
Cells. 2023 Dec 30;13(1):80. doi: 10.3390/cells13010080.
Mesenchymal stem cells (MSCs) ameliorate T-and B cell-mediated immune responses. In particular, tonsil-MSCs (T-MSCs) are attractive candidates for practical and clinical applications because of their ease of acquisition and relatively low immunogenicity compared with other MSC sources. The use of MSCs as a therapeutic tool in atopic dermatitis (AD) has been investigated, but that of T-MSCs remains to be explored. Therefore, we investigated the immunomodulatory effects of primed T-MSCs in AD pathogenesis. In our animal study, primed T-MSCs showed greater immunological suppressive effects than naïve T-MSCs. Additionally, in vitro, the proliferation of B cells was downregulated by the addition of primed T-MSCs compared with naïve T-MSCs. The activation of B cells to differentiate into antibody-secreting cells and produce IgE was also reduced when primed T-MSCs were added. Moreover, under CD40-knockdown conditions, we found that CD40 in primed T-MSCs played a critical role as a regulator of B cell activation and was mediated by the non-canonical NF-κB pathway. Therefore, our findings suggest a promising role for primed T-MSCs in the treatment of AD by regulating B cell-mediated inflammatory responses, which are dependent on CD40 expression on primed T-MSCs mediated through the non-canonical NF-κB pathway.
间充质干细胞 (MSCs) 可改善 T 细胞和 B 细胞介导的免疫反应。特别是,扁桃体间充质干细胞 (T-MSCs) 由于易于获取且与其他 MSC 来源相比免疫原性相对较低,因此成为实用和临床应用的有吸引力的候选者。已经研究了将 MSCs 用作特应性皮炎 (AD) 的治疗工具,但 T-MSCs 的用途仍有待探索。因此,我们研究了致敏 T-MSCs 在 AD 发病机制中的免疫调节作用。在我们的动物研究中,致敏 T-MSCs 表现出比幼稚 T-MSCs 更强的免疫抑制作用。此外,在体外,与幼稚 T-MSCs 相比,添加致敏 T-MSCs 可下调 B 细胞的增殖。当添加致敏 T-MSCs 时,B 细胞向产生抗体的细胞分化并产生 IgE 的激活也减少。此外,在 CD40 敲低条件下,我们发现致敏 T-MSCs 中的 CD40 作为 B 细胞激活的调节剂发挥关键作用,并且通过非经典 NF-κB 途径介导。因此,我们的研究结果表明,致敏 T-MSCs 通过调节 B 细胞介导的炎症反应在 AD 治疗中具有广阔的应用前景,该反应依赖于致敏 T-MSCs 上的 CD40 表达,通过非经典 NF-κB 途径介导。