Adipose-derived stem cells ameliorate atopic dermatitis by suppressing the IL-17 expression of Th17 cells in an ovalbumin-induced mouse model.
Adipose-derived stem cells ameliorate atopic dermatitis by suppressing the IL-17 expression of Th17 cells in an ovalbumin-induced mouse model.
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DOI：
10.1186/s13287-022-02774-7
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发表时间：
2022-03-07
影响因子：
7.5
通讯作者：
Feng J
中科院分区：
文献类型：
--
作者：
Guan J;Li Y;Lu F;Feng J
间充质干细胞（MSCs）由于其免疫调节作用而具有治疗特应性皮炎（AD）的潜力。然而，与MSC对AD的治疗功效相关的潜在机制是多样的，并且与细胞类型和递送方法两者相关。本研究采用卵清蛋白（OVA）诱导的AD小鼠模型，探讨脂肪干细胞（ADSCs）对AD的治疗作用及其机制。AD小鼠皮下注射小鼠ADSC、可的松或PBS，通过大体和组织学检查以及血清IgE水平来确定治疗效果。此外，进行皮肤样品的qPCR、RNA测序分析以及ADSC和Th 17细胞的共培养以探索潜在的治疗机制。ADSC治疗减轻了AD病理，降低了血清IgE水平，并减少了模型小鼠皮肤中肥大细胞的浸润。此外，在ADSC和可的松治疗组中，IL-4 R和Th 17相关产物（IL-17 A，CCL 20和MMP 12）的组织水平受到抑制。基因组学和生物信息学分析表明，在ADSC和可的松治疗组的下调基因中，炎症相关通路显著富集，特别是IL-17信号通路。共培养实验显示，ADSCs显著抑制Th 17细胞的增殖和促炎细胞因子IL-17 A和RORγT的表达。此外，PD-L1、TGF-β和PGE 2的表达水平在共培养的ADSC中相对于在单培养的ADSC中显著上调。ADSC主要通过下调Th 17细胞分泌IL-17来改善OVA诱导的小鼠AD。在线版本包含补充材料，可通过10.1186/s13287-022-02774-7获得。
Mesenchymal stem cells (MSCs) have therapeutic potential for atopic dermatitis (AD) owing to their immunoregulatory effects. However, the underlying mechanisms associated with the therapeutic efficacy of MSCs on AD are diverse and related to both cell type and delivery method. This study investigated the therapeutic effect and mechanisms of adipose-derived stem cells (ADSCs) on AD using an ovalbumin (OVA)-induced AD mouse model. AD mice were subcutaneously injected with mouse ADSCs, cortisone, or PBS, and the therapeutic effects were determined by gross and histological examinations and serum IgE levels. Additionally, qPCR, RNA-sequencing analyses of skin samples and co-culture of ADSCs and Th17 cells were conducted to explore the underlying therapeutic mechanisms. ADSCs treatment attenuated the AD pathology, decreased the serum IgE levels, and decreased mast cells infiltration in the skin of the model mice. Moreover, tissue levels of IL-4R and Th17-relevant products (IL-17A, CCL20, and MMP12) were suppressed in the ADSC- and cortisone-treated groups. Genomics and bioinformatics analyses demonstrated significant enrichment of inflammation-related pathways in the downregulated genes of the ADSC- and cortisone-treated groups, specifically the IL-17 signaling pathway. Co-culture experiments revealed that ADSCs significantly suppressed the proliferation of Th17 cells and the expression of proinflammatory cytokines (IL-17A and RORγT). Furthermore, expression levels of PD-L1, TGF-β, and PGE2 were significantly upregulated in co-cultured ADSCs relative to those in monocultured ADSCs. ADSCs ameliorate OVA-induced AD in mice mainly by downregulating IL-17 secretion of Th17 cells. The online version contains supplementary material available at 10.1186/s13287-022-02774-7.
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DOI：
10.1038/jid.2009.65
发表时间：
2009-09
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.4
作者：
Duffy, Michelle M.;Pindjakova, Jana;Griffin, Matthew D.
通讯作者：
Griffin, Matthew D.
影响因子：
1.2
作者：
Flaherty, Stephanie;Reynolds, Joseph M.
通讯作者：
Reynolds, Joseph M.
影响因子：
12.4
作者：
Apfelbacher, C. J.;Diepgen, T. L.;Schmitt, J.
通讯作者：
Schmitt, J.
影响因子：
7
作者：
Kawakami T;Ando T;Kimura M;Wilson BS;Kawakami Y
通讯作者：
Kawakami Y