Stanniocalcin-2 contributes to mesenchymal stromal cells attenuating murine contact hypersensitivity mainly via reducing CD8+ Tc1 cells

Liu, Qiuli; Huang, Weijun; Cai, Chuang; Xia, Wenjie; Peng, Yanwen; Zheng, Shuwei; Li, Gang; Xu, Yan; Wang, Jiancheng; Liu, Chang; Zhang, Xiaoran; Huang, Li; Xiang, Andy Peng; Zhang, Qi

doi:10.1038/s41419-018-0614-x

Cited by 24 publications

(28 citation statements)

References 49 publications

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“…The results of this study showed that infiltration of CD8 + T cells was decreased in ALI mice treated with MSCs, in turn indicating that LPS-induced ALI ameliorated by MSCs was associated with a reduction of CD8 + T cells. In previous studies, MSCs, and their production of indoleamine 2,3 dioxygenase, were shown to contribute to the induction of apoptosis in activated T cells 32,33 and high stanniocalcin-2 expression decreased CD8 + cytotoxic T cells during MSC-based treatment for allergic contact dermatitis 15 . Taken together, our results indicate that MSCs may help prevent or treat ALI by affecting CD8 + T cells.…”

Section: Discussionmentioning

confidence: 97%

“…MSCs have been reported to regulate many aspects of the T-cell response, including proliferation, survival, and differentiation 14 . In previous studies, MSCs were shown to reduce CD8 + cytotoxic T cells via stanniocalcin-2 and to alleviate the inflammatory reaction in mice 15 . Ronit et al 16 reported the recruitment of CD8 + T cells following LPS-induced lung injury.…”

Section: Introductionmentioning

confidence: 95%

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Mesenchymal stem cells alleviate LPS-induced acute lung injury by inhibiting the proinflammatory function of Ly6C+ CD8+ T cells

Zhu

Feng

et al. 2020

Cell Death Dis

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Systemic inflammatory processes, including alveolar injury, cytokine induction, and neutrophil accumulation, play key roles in the pathophysiology of acute lung injury (ALI). The immunomodulatory effects of mesenchymal stem cells (MSCs) can contribute to the treatment of inflammatory disorders. In previous studies, the focus was on innate immune cells and the effects of MSCs on ALI through CD8+ T cells remain unclear. In the present study, lipopolysaccharide (LPS) was used to induce ALI in mice. ALI mice were treated with MSCs via intratracheal instillation. Survival rate, histopathological changes, protein levels, total cell count, cytokine levels, and chemokine levels in alveolar lavage fluid were used to determine the efficacy of MSCs. Mass cytometry and single-cell RNA sequencing (scRNA-seq) were used to characterize the CD8+ T cells in the lungs. Ly6C− CD8+ T cells are prevalent in normal mice, whereas a specialized effector phenotype expressing a high level of Ly6C is predominant in advanced disease. MSCs significantly mitigated ALI and improved survival. MSCs decreased the infiltration of CD8+ T cells, especially Ly6C+ CD8+ T cells into the lungs. Mass cytometry revealed that CD8+ T cells expressing high Ly6C and CXCR3 levels caused tissue damage in the lungs of ALI mice, which was alleviated by MSCs. The scRNA-seq showed that Ly6C+ CD8+ T cells exhibited a more activated phenotype and decreased expression of proinflammatory factors that were enriched the most in immune chemotaxis after treatment with MSCs. We showed that CD8+ T cells play an important role in MSC-mediated ALI remission, and both infiltration quantity and proinflammatory function were inhibited by MSCs, indicating a potential mechanism for therapeutic intervention.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 95%

Mesenchymal stem cells alleviate LPS-induced acute lung injury by inhibiting the proinflammatory function of Ly6C+ CD8+ T cells

Zhu

Feng

et al. 2020

Cell Death Dis

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“…These models involve an initial application of chemical sensitiser, followed by a challenge with the same chemical several days later to elicit a robust T cellmediated inflammatory response featuring immune cell recruitment and swelling (Deane & Hickey 2009, Deane et al 2012. MSC from bone marrow (Chen et al 2018), adipose tissue (Kikuchi et al 2017) and gingiva (Su et al 2011, Li et al 2016 have the ability to inhibit ear swelling in contact sensitivity when delivered via and intravenous route. In contrast, eMSCs did not inhibit ear swelling in an oxazolone-induced model of contact sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Endometrial mesenchymal stem/stromal cell modulation of T cell proliferation

et al. 2018

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Perivascular mesenchymal stem/stromal cells can be isolated from the human endometrium using the surface marker SUSD2 and are being investigated for use in tissue repair. Mesenchymal stem/stromal cells from other tissues modulate T cell responses via mechanisms including interleukin-10, prostaglandin E2, TGF-β1 and regulatory T cells. Animal studies demonstrate that endometrial mesenchymal stem/stromal cells can also modify immune responses to implanted mesh, but the mechanism/s they employ have not been explored. We examined the immunomodulatory properties of human endometrial mesenchymal stem/stromal cells on lymphocyte proliferation using mouse splenocyte cultures. Endometrial mesenchymal stem/stromal cells inhibited mitogen-induced lymphocyte proliferation in vitro in a dose-dependent manner. Inhibition of lymphocyte proliferation was not affected by blocking the mouse interleukin-10 receptor or inhibiting prostaglandin production. Endometrial mesenchymal stem/stromal cells continued to restrain lymphocyte proliferation in the presence of an inhibitor of TGF-β receptors, despite a reduction in regulatory T cells. Thus, the in vitro inhibition of mitogen-induced lymphocyte proliferation by endometrial mesenchymal stem/stromal cells occurs by a mechanism distinct from the interleukin-10, prostaglandin E2, TGF-β1 and regulatory T cell-mediated mechanisms employed by MSC from other tissues. eMSCs were shown to produce interleukin-17A and Dickkopf-1 which may contribute to their immunomodulatory properties. In contrast to MSC from other sources, systemic administration of endometrial mesenchymal stem/stromal cells did not inhibit swelling in a T cell-mediated model of skin inflammation. We conclude that, while endometrial mesenchymal stem/stromal cells can modify immune responses, their immunomodulatory repertoire may not be sufficient to restrain some T cell-mediated inflammatory events.Reproduction (2019) 157 43-52

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“…Importantly, it has to be noted that ASCs were conversely less potent than BM-MSCs at preventing NK cell proliferation, in agreement with the lack of reversion of MSC-dependent NK-suppressive activity by IDO inhibitors. 44,45 In addition, BM-MSCs overexpressed PD-L1/CD274…”

Section: Bm-mscs and Ascs Differentially Elicit Immune Response Supmentioning

confidence: 99%

“…and staniocalcin-2 (STC2), two suppressive molecules affecting CD8 pos T-cell activation and synthesis of inflammatory cytokines. 44,45 Of note, we restrained our study to lean MSC donors to avoid any confounding impact of obesity. In fact, cultured ASCs obtained from obese patients were reported to display reduced immunosuppressive activities in classical in vitro assays.…”

Section: Bm-mscs and Ascs Differentially Elicit Immune Response Supmentioning

confidence: 99%

Integrated transcriptomic, phenotypic, and functional study reveals tissue-specific immune properties of mesenchymal stromal cells

et al. 2019

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Clinical-grade mesenchymal stromal cells (MSCs) can be expanded from bone marrow and adipose tissue to treat inflammatory diseases and degenerative disorders. However, the influence of their tissue of origin on their functional properties, including their immunosuppressive activity, remains unsolved. In this study, we produced paired bone marrow-derived mesenchymal stromal cell (BM-MSC) and adiposederived stromal cell (ASC) batches from 14 healthy donors. We then compared them using transcriptomic, phenotypic, and functional analyses and validated our results on purified native MSCs to infer which differences were really endowed by tissue of origin. Cultured MSCs segregated together owing to their tissue of origin based on their gene expression profile analyzed using differential expression and weighted gene coexpression network analysis. This translated into distinct immune-related gene signatures, phenotypes, and functional cell interactions. Importantly, sorted native BM-MSCs and ASCs essentially displayed the same distinctive patterns than their in vitro-expanded counterparts. As a whole, ASCs exhibited an immune profile consistent with a stronger inhibition of immune response and a lower immunogenicity, supporting the use of adipose tissue as a valuable source for clinical applications.

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Stanniocalcin-2 contributes to mesenchymal stromal cells attenuating murine contact hypersensitivity mainly via reducing CD8+ Tc1 cells

Cited by 24 publications

References 49 publications

Mesenchymal stem cells alleviate LPS-induced acute lung injury by inhibiting the proinflammatory function of Ly6C+ CD8+ T cells

Mesenchymal stem cells alleviate LPS-induced acute lung injury by inhibiting the proinflammatory function of Ly6C+ CD8+ T cells

Endometrial mesenchymal stem/stromal cell modulation of T cell proliferation

Integrated transcriptomic, phenotypic, and functional study reveals tissue-specific immune properties of mesenchymal stromal cells

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