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人脐血来源的髓系抑制细胞在特应性皮炎中的皮肤修复和免疫调节作用。

Skin repair and immunoregulatory effects of myeloid suppressor cells from human cord blood in atopic dermatitis.

机构信息

ViMedier Platform Group, ViGenCell Inc., Seoul, Republic of Korea.

Department of Dermatology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

出版信息

Front Immunol. 2024 Jan 9;14:1263646. doi: 10.3389/fimmu.2023.1263646. eCollection 2023.

DOI:10.3389/fimmu.2023.1263646
PMID:38264643
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10803405/
Abstract

INTRODUCTION

Previously, we achieved large-scale expansion of bone marrow-derived suppressor cells (MDSCs) derived from cluster of differentiation (CD)34 cells cultured in human umbilical cord blood (hUCB) and demonstrated their immunomodulatory properties. In the present study, we assessed the therapeutic efficacy of hUCB-MDSCs in atopic dermatitis (AD).

METHODS

(Df)-induced NC/Nga mice (clinical score of 7) were treated with hUCB-MDSCs or a control drug. The mechanisms underlying the therapeutic effects of hUCB-MDSCs were evaluated.

RESULTS AND DISCUSSION

hUCB-MDSCs demonstrated immunosuppressive effects in both human and mouse CD4 T cells. hUCB-MDSCs significantly reduced the clinical severity scores, which were associated with histopathological changes, and reduced inflammatory cell infiltration, epidermal hyperplasia, and fibrosis. Furthermore, hUCB-MDSCs decreased the serum levels of immunoglobulin E, interleukin (IL)-4, IL-5, IL-13, IL-17, thymus- and activation-regulated chemokines, and thymic stromal lymphopoietin. Additionally, they altered the expression of the skin barrier function-related proteins filaggrin, involucrin, loricrin, cytokeratin 10, and cytokeratin 14 and suppressed the activation of Df-restimulated T-cells via cell-cell interactions. hUCB-MDSCs promoted skin recovery and maintained their therapeutic effect even after recurrence. Consequently, hUCB-MDSC administration improved Df-induced AD-like skin lesions and restored skin barrier function. Our findings support the potential of hUCB-MDSCs as a novel treatment strategy for AD.

摘要

简介

此前，我们成功地从人脐血（hUCB）中培养的分化群（CD）34 细胞中大规模扩增骨髓来源的抑制细胞（MDSCs），并证明了它们的免疫调节特性。在本研究中，我们评估了 hUCB-MDSC 在特应性皮炎（AD）中的治疗效果。

方法

（Df）诱导的 NC/Nga 小鼠（临床评分 7）用 hUCB-MDSC 或对照药物治疗。评估 hUCB-MDSC 治疗效果的机制。

结果与讨论

hUCB-MDSC 在人和小鼠 CD4 T 细胞中均具有免疫抑制作用。hUCB-MDSC 显著降低临床严重程度评分，与组织病理学变化相关，并减少炎症细胞浸润、表皮增生和纤维化。此外，hUCB-MDSC 降低了血清免疫球蛋白 E、白细胞介素（IL）-4、IL-5、IL-13、IL-17、胸腺激活调节趋化因子和胸腺基质淋巴细胞生成素的水平。此外，它们改变了皮肤屏障功能相关蛋白丝聚合蛋白、兜甲蛋白、内披蛋白、角蛋白 10 和角蛋白 14 的表达，并通过细胞-细胞相互作用抑制 Df 刺激的 T 细胞的激活。hUCB-MDSC 促进皮肤恢复，并在复发后仍保持治疗效果。因此，hUCB-MDSC 给药改善 Df 诱导的 AD 样皮肤损伤并恢复皮肤屏障功能。我们的研究结果支持 hUCB-MDSC 作为 AD 新型治疗策略的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18e0/10803405/13ae4bac3ef1/fimmu-14-1263646-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18e0/10803405/ef0f00eddc08/fimmu-14-1263646-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18e0/10803405/6d5bd23880b5/fimmu-14-1263646-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18e0/10803405/bfae7a202f94/fimmu-14-1263646-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18e0/10803405/4f07167e7f6a/fimmu-14-1263646-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18e0/10803405/13ae4bac3ef1/fimmu-14-1263646-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18e0/10803405/ef0f00eddc08/fimmu-14-1263646-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18e0/10803405/8d146885902e/fimmu-14-1263646-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18e0/10803405/0b1722fe8e46/fimmu-14-1263646-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18e0/10803405/06f0cd9d2491/fimmu-14-1263646-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18e0/10803405/6d5bd23880b5/fimmu-14-1263646-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18e0/10803405/bfae7a202f94/fimmu-14-1263646-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18e0/10803405/4f07167e7f6a/fimmu-14-1263646-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18e0/10803405/13ae4bac3ef1/fimmu-14-1263646-g008.jpg

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