Minor salivary gland mesenchymal stromal cells derived from patients with Sjӧgren's syndrome deploy intact immune plasticity.
Minor salivary gland mesenchymal stromal cells derived from patients with Sjӧgren's syndrome deploy intact immune plasticity.
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DOI：
10.1016/j.jcyt.2020.09.008
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发表时间：
2021-04
期刊：
影响因子：
4.5
通讯作者：
Galipeau J
中科院分区：
文献类型：
--
作者：
McCoy SS;Giri J;Das R;Paul PK;Pennati A;Parker M;Liang Y;Galipeau J
间充质基质细胞（MSC）为小涎腺（MSG）提供上皮腺体组织的支持和龛细胞。关于原发性干燥综合征（pSS）中的常驻MSG衍生的MSC（MSG-MSC）知之甚少。我们的目标是确定内源性pSS MSG-MSC的免疫生物学。使用从同意的pSS受试者（n=13）分离的培养适应的MSG-MSC，我们进行了与对照相比的pSS MSG-MSC免疫生物学和整体基因表达的体外询问。为此，我们进行了吲哚胺2，3-双加氧酶（IDO）、程序性死亡配体1（PD-L1）和细胞间粘附标志物1（ICAM-1）在干扰素（IFN）γ许可前后的表型和免疫功能分析，以及MSG-MSCs对T细胞增殖的影响。考虑到pSS的女性优势，我们还讨论了17 β-雌二醇对雌激素受体α+相关MSC功能的影响。我们发现，MSG-MSC在IFNγ刺激后发挥了正常的免疫调节功能，如IDO、PD-L1和ICAM-1的蛋白质水平表达增加所证明的。我们还发现，MSG-MSC以剂量依赖性方式抑制T细胞增殖，与17 β-雌二醇暴露无关。基因本体和途径分析强调细胞外基质沉积是pSS和对照MSG-MSC之间的可能差异。MSG-MSC在pSS中表现出增加的αSMA表达，表明部分成肌纤维细胞样适应。这些发现确立了MSG-MSC在pSS和对照患者中的类似免疫调节功能，排除了pSS中固有的MSC免疫调节缺陷。pSS MSG-MSC显示出部分印记的成肌纤维细胞样表型，其可能在慢性炎症的情况下出现，为pSS相关的腺纤维化提供了合理的病因学。
Mesenchymal stromal cells (MSCs) provide minor salivary glands (MSGs) with support and niche cells for epithelial glandular tissue. Little is known about resident MSG derived MSCs (MSG-MSCs) in primary Sjӧgren’s syndrome (pSS). Our objective is to define the immunobiology of endogenous pSS MSG-MSCs. Using culture adapted MSG-MSCs isolated from consenting pSS subjects (n=13), we performed in vitro interrogation of pSS MSG-MSC immunobiology and global gene expression compared to controls. To this end, we performed phenotypic and immune functional analysis of indoleamine 2,3-dioxygenase (IDO), programmed death-ligand 1 (PD-L1), and intercellular adhesion marker-1 (ICAM-1) before and after interferon (IFN)γ licensing as well as the effect of MSG-MSCs on T cell proliferation. Considering the female predominance of pSS, we also addressed the influence of 17 β-estradiol on estrogen receptorα+-related MSC function. We found that MSG-MSCs deploy normal immunoregulatory functionality after IFNγ stimulation as demonstrated by increased protein-level expression of IDO, PD-L1, and ICAM-1. We also found that MSG-MSCs suppressed T cell proliferation in a dose-dependent manner independent of 17 β-estradiol exposure. Gene ontology and pathway analysis highlighted extracellular matrix deposition as a possible difference between pSS and control MSG-MSCs. MSG-MSCs demonstrate increased αSMA expression in pSS indicating a partial myofibroblast-like adaptation. These findings establish similar immunoregulatory function of MSG-MSCs in both pSS and control patients precluding intrinsic MSC immune regulatory defects in pSS. pSS MSG-MSCs show a partial imprinted myofibroblast-like phenotype which may arise in the setting of chronic inflammation, providing a plausible etiology for pSS related glandular fibrosis.
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影响因子：
7.8
作者：
Gitelman, S E;Kobrin, M S;Ye, J Q;Lopez, A R;Lee, A;Derynck, R
通讯作者：
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发表时间：
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影响因子：
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