Immunologic regulatory effects of human umbilical cord blood‐derived mesenchymal stem cells in a murine ovalbumin asthma model

Kang, Sung Yoon; Park, D.-E.; Song, Woo Jung; Bae, Boram; Lee, J.-W.; Sohn, Kyung Hee; Lee, H.-S.; Kang, Hye Ryun; Park, H.-W.; Chang, Young-Il; Choi, Soo Jin; Oh, Won‐Seok; Min, Kyung Up; Cho, Sang Heon

doi:10.1111/cea.12920

Cited by 26 publications

(21 citation statements)

References 40 publications

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“…IL-4 can lead to changes in functions of allergic asthma including eosinophil infiltration, airway hyperresponsiveness and mucus overproduction. 42,43 Our results showed that expression of IL-4 decreased following Del-1 administration (Figure 4). It has been recognized that CCL11(eotaxin), a small cytokine belonging to the CC chemokine family, selectively recruits eosinophils by inducing their chemotaxis in allergic asthma.…”

Section: Discussionmentioning

confidence: 74%

Developmental endothelial locus‐1 (Del‐1) antagonizes Interleukin‐17‐mediated allergic asthma

et al. 2018

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Interleukin (IL)-17 is a major contributor to the pathogenesis of allergic asthma. Developmental endothelial locus-1 (Del-1) is an endothelial cell-secreted protein known to inhibit IL-17 expression. However, little is known about the association between Del-1 and IL-17 in the pathogenesis of allergic asthma. Using bronchoalveolar lavage fluid (BALF) and peripheral blood samples collected from allergic asthmatic patients and controls, we explored the role of Del-1 in relation to IL-17 in allergic asthma. We found that the negative correlation between Del-1 and IL-17 was significant in BALF of allergic asthmatics. Del-1 treatment inhibited the expression of IL-17, the differentiation of IL-17-secreting leukocytes and associated cytokines. Contrarily, IL-17 levels were increased after treatment with anti-Del-1 mAb. Consistent with this, Del-1 treatment led to downregulation of IL-5, CCL5 and IL-4, thus reducing secretion of eosinophil cationic protein. Furthermore, Del-1 significantly downregulated the expression of ICAM-1 and may have the potential to reduce leukocyte transendothelial migration. Our data demonstrate that Del-1 can negatively regulate IL-17 and its proinflammatory function, thereby limiting airway inflammation in allergic asthmatics, and suggest Del-1 as a potential candidate for prevention and treatment of allergic asthma.

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Section: Discussionmentioning

confidence: 74%

Developmental endothelial locus‐1 (Del‐1) antagonizes Interleukin‐17‐mediated allergic asthma

et al. 2018

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“…The hUC-MSCs can reduce ovalbumin (OVA)-induced allergic inflammation. This effect might be mediated by regulatory T (Treg) cells ( Kang et al, 2017 ). Human mesenchymal stem cells (HUMSCs) can reduce neutrophil airway inflammation by downregulating neutrophil chemokine production and by modulating T-cell responses ( Hong et al, 2017 ).…”

Section: Resultsmentioning

confidence: 99%

Human Adipose Tissue-Derived Mesenchymal Stem Cells Attenuate Atopic Dermatitis by Regulating the Expression of MIP-2, miR-122a-SOCS1 Axis, and Th1/Th2 Responses

Kim

Lee²,

Kim

et al. 2018

Front. Pharmacol.

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The objective of this study was to investigate the effect of human adipose tissue-derived mesenchymal stem cells (AdMSCs) on atopic dermatitis (AD) in the BALB/c mouse model. The AdMSCs attenuated clinical symptoms associated with AD, decreased numbers of degranulated mast cells (MCs), IgE level, amount of histamine released, and prostaglandin E2 level. Atopic dermatitis increased the expression levels of cytokines/chemokines, such as interleukin-5 (IL-5), macrophage inflammatory protein-1ß (MIP-1ß), MIP-2, chemokine (C-C motif) ligand 5 (CCL5), and IL-17, in BALB/c mouse. The AdMSCs showed decreased expression levels of these cytokines in the mouse model of AD. In vivo downregulation of MIP-2 attenuated the clinical symptoms associated with AD. Atopic dermatitis increased the expression levels of hallmarks of allergic inflammation, induced interactions of Fc𝜀RIβ with histone deacetylase 3 (HDAC3) and Lyn, increased ß-hexosaminidase activity, increased serum IgE level, and increased the amount of histamine released in an MIP-2-dependent manner. Downregulation of MIP-2 increased the levels of several miRNAs, including miR-122a-5p. Mouse miR-122a-5p mimic inhibited AD, while suppressor of cytokine signaling 1 (SOCS1), a predicted downstream target of miR-122a-5p, was required for AD. The downregulation of SOCS1 decreased the expression levels of MIP-2 and chemokine (C-X-C motif) ligand 13 (CXCL13) in the mouse model of AD. The downregulation of CXCL13 attenuated AD and allergic inflammation such as passive cutaneous anaphylaxis. The role of T cell transcription factors in AD was also investigated. Atopic dermatitis increased the expression levels of T-bet and GATA-3 [transcription factors of T-helper 1 (Th1) and T-helper 2 (Th2) cells, respectively] but decreased the expression of Foxp3, a transcription factor of regulatory T (Treg) cells, in an SOCS1-dependent manner. In addition to this, miR-122a-5p mimic also prevented AD from regulating the expression of T-bet, GATA-3, and Foxp3. Atopic dermatitis increased the expression of cluster of differentiation 163 (CD163), a marker of M2 macrophages, but decreased the expression of inducible nitric oxide synthase (iNOS), a marker of M1 macrophages. Additionally, SOCS1 and miR-122a-5p mimic regulated the expression of CD163 and iNOS in the mouse model of AD. Experiments employing conditioned medium showed interactions between MCs and macrophages in AD. The conditioned medium of AdMSCs, but not the conditioned medium of human dermal fibroblasts, negatively inhibited the features of allergic inflammation. In summary, we investigated the anti-atopic effects of AdMSCs, identified targets of AdMSCs, and determined the underlying mechanism for the anti-atopic effects of AdMSCs.

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“…UCB-MSC has a multidirectional immunomodulatory effect on both innate and adaptive immune cells: T lymphocytes and B lymphocytes, dendritic cells and natural killer cells. UCB-MSC exhibit immunosuppressive activity on lymphocyte proliferation and inhibit the pro-inflammatory effect of cytokines [6]. Hu et al (2013) in the results of their research indicate the clinical safety of using Wharton's jelly-derived mesenchymal stem cells from the umbilical cord of patients, as well as the restoration of pancreatic B-cell function in newly diagnosed type I diabetes [7].…”

Section: Treating Type I Diabetesmentioning

confidence: 99%

Current state of umbilical cord stem cells in humans

Borys-Wójcik

Moncrieff

Kempisty

et al. 2019

Medical Journal of Cell Biology

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The umbilical cord is an unlimited source of mesenchymal stem cells (MSC) and hematopoietic stem cells (HSC). MSC obtained from the umbilical cord can be differentiated into different types of mesodermal cells, e.g. chondrocytes, osteocytes, adipocytes, and myocytes. It is also worth mentioning that there are reports of MSC differentiation into endo and ectodermal cells. The immunosuppressive properties of MSCs can protect against graft versus host disease as well as prevent rejection after transplantation. Umbilical cord stem cells can be frozen and then stored in liquid nitrogen for many years. In this work, we focused on the use of preclinical and clinical umbilical cord stem cells in disease entities such as type I diabetes, chronic renal failure, and multiple sclerosis. Furthermore, the anti-cancer properties of Wharton's jelly cells are described. Running title: Umbilical cord stem cells in humans

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Immunologic regulatory effects of human umbilical cord blood‐derived mesenchymal stem cells in a murine ovalbumin asthma model

Abstract: Our results suggest that huMSC treatment reduces OVA-induced allergic inflammation, which could be mediated by regulatory T cells.

Cited by 26 publications

References 40 publications

Developmental endothelial locus‐1 (Del‐1) antagonizes Interleukin‐17‐mediated allergic asthma

Developmental endothelial locus‐1 (Del‐1) antagonizes Interleukin‐17‐mediated allergic asthma

Human Adipose Tissue-Derived Mesenchymal Stem Cells Attenuate Atopic Dermatitis by Regulating the Expression of MIP-2, miR-122a-SOCS1 Axis, and Th1/Th2 Responses

Current state of umbilical cord stem cells in humans

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