Multipotent adult progenitor cells induce regulatory T cells and promote their suppressive phenotype via TGFβ and monocyte-dependent mechanisms.
Multipotent adult progenitor cells induce regulatory T cells and promote their suppressive phenotype via TGFβ and monocyte-dependent mechanisms.
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DOI：
10.1038/s41598-021-93025-x
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发表时间：
2021-06-30
影响因子：
4.6
通讯作者：
Ting AE
中科院分区：
文献类型：
--
作者：
Valentin-Torres A;Day C;Taggart JM;Williams N;Stubblefield SR;Roobrouck VD;Beyens J;Ting AE
免疫系统的失调可以引发慢性炎症反应，加剧疾病病理。多能成体祖细胞（MAPC细胞），一种成体贴壁骨髓源性基质细胞，已被观察到在多种临床病症中促进不受控制的炎症反应的消退，所述临床病症包括急性缺血性中风、急性心肌梗死（AMI）、移植物抗宿主病（GvHD）和急性呼吸窘迫综合征（ARDS）。MAPC细胞调节免疫应答的机制之一是通过诱导调节性T细胞（Tcells），然而，所涉及的机制仍有待充分阐明。在本文中，我们证明，在体外环境中，MAPC细胞通过促进Treg增殖和CD 4 + T细胞分化为T细胞来增加Treg频率。此外，MAPC细胞诱导的T细胞增殖（miT细胞增殖）具有更强的抑制性表型，其特征在于CTLA-4、HLA-DR和PD-L1的表达增加以及T细胞抑制能力。MAPC细胞还通过诱导CD 45 RA + CD 45 RO+过渡性T细胞来促进Treg活化。此外，我们鉴定了转化生长因子β（TGFβ）作为MAPC细胞分泌的Treg诱导的必需因子。此外，吲哚胺2，3-双加氧酶（IDO）的抑制导致MAPC细胞的Treg诱导减少，证明IDO参与。我们的研究还表明，CD 14+单核细胞在MAPC细胞诱导Treg中起关键作用。我们的研究描述了MAPC细胞依赖性Treg表型变化，并提供了MAPC细胞促进Treg分化的潜在机制的证据。
Dysregulation of the immune system can initiate chronic inflammatory responses that exacerbate disease pathology. Multipotent adult progenitor cells (MAPC cells), an adult adherent bone-marrow derived stromal cell, have been observed to promote the resolution of uncontrolled inflammatory responses in a variety of clinical conditions including acute ischemic stroke, acute myocardial infarction (AMI), graft vs host disease (GvHD), and acute respiratory distress syndrome (ARDS). One of the proposed mechanisms by which MAPC cells modulate immune responses is via the induction of regulatory T cells (Tregs), however, the mechanism(s) involved remains to be fully elucidated. Herein, we demonstrate that, in an in vitro setting, MAPC cells increase Treg frequencies by promoting Treg proliferation and CD4+ T cell differentiation into Tregs. Moreover, MAPC cell-induced Tregs (miTregs) have a more suppressive phenotype characterized by increased expression of CTLA-4, HLA-DR, and PD-L1 and T cell suppression capacity. MAPC cells also promoted Treg activation by inducing CD45RA+ CD45RO+ transitional Tregs. Additionally, we identify transforming growth factor beta (TGFβ) as an essential factor for Treg induction secreted by MAPC cells. Furthermore, inhibition of indoleamine 2, 3-dioxygenase (IDO) resulted in decreased Treg induction by MAPC cells demonstrating IDO involvement. Our studies also show that CD14+ monocytes play a critical role in Treg induction by MAPC cells. Our study describes MAPC cell dependent Treg phenotypic changes and provides evidence of potential mechanisms by which MAPC cells promote Treg differentiation.
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影响因子：
20.3
作者：
Highfill, Steven L.;Kelly, Ryan M.;Blazar, Bruce R.
通讯作者：
Blazar, Bruce R.
影响因子：
7.3
作者：
Churlaud G;Pitoiset F;Jebbawi F;Lorenzon R;Bellier B;Rosenzwajg M;Klatzmann D
通讯作者：
Klatzmann D
影响因子：
4.4
作者：
Baecher-Allan, Clare;Wolf, Elizabeth;Haller, David A.
通讯作者：
Haller, David A.
DOI：
10.1038/s41573-019-0041-4
发表时间：
2019-10
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Ferreira LMR;Muller YD;Bluestone JA;Tang Q
通讯作者：
Tang Q
DOI：
10.1084/jem.20090847
发表时间：
2009-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Francisco LM;Salinas VH;Brown KE;Vanguri VK;Freeman GJ;Kuchroo VK;Sharpe AH
通讯作者：
Sharpe AH