Adipose-derived stromal cell immunosuppression of T cells is enhanced under “physiological” hypoxia

Горностаева, А. Н.; Бобылева, П. И.; Andreeva, E. R.; Yakubets, D.A.; Буравкова, Л. Б.

doi:10.1016/j.tice.2019.101320

Cited by 18 publications

(22 citation statements)

References 39 publications

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“…Such finding suggests that the milieu of T2D strongly compromises the potential of AT-MSC to downmodulate CD25 expression and accordingly activation of PBMC. We also monitored the expression of the late activation marker HLA-DR, which causes the involvement of immune cells in the "graft-versus-host" reaction 42 . Allogeneic nAT-MSC reduce its expression with a significantly attenuated potential in co-culture with dPBMC, relative to nPBMC.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Properties of Human Adipose Mesenchymal Stromal/Stem Cell in Type 2 Diabetes Milieu.

Elshahat

Abu-Shahba²,

El-Din³

et al. 2023

Azhar International Journal of Pharmaceutical and Medical Scien

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Adipose tissue is a readily available and plentiful source of multipotent mesenchymal stromal/stem cells (AT-MSC). The immunomodulatory properties of AT-MSC are being introduced in type 2 diabetes (T2D) cell-based therapy. The study aimed to uncover the impact of T2D, on the interplay between AT-MSC and immune cells to develop an effective and safe AT-MSC immunotherapeutic modality. Thus, a direct allogenic co-culture of healthy AT-MSC (nAT-MSC) and peripheral blood mononuclear cells (PBMC), from healthy (nPBMC) or T2D (dPBMC) donors, and stimulated with anti-CD3/CD28, was established in vitro. PBMC proliferation was evaluated by measuring 5-bromo-20-deoxyuridine (Brdu) incorporation in the DNA of proliferating cells in a colorimetric ELISA assay. Expression levels of CD3 + T cell activation surface markers (CD25 and HLA-DR) were detected using a flow cytometer. As well, the anti-proliferative effect of naïve and interferon gamma (IFN-ɤ) -primed AT-MSC, isolated from T2D patients (dAT-MSC), on autologous PBMC was explored using the Brdu proliferation assay. In the applied co-culture setting, the diabetic milieu does not significantly impact the potential of nAT-MSC to suppress stimulated PBMC proliferation. However, it significantly compromises nAT-MSC ability to modulate the activation markers expression, making them less potent to suppress CD25 and HLA-DR expression. Moreover, the dAT-MSC have attenuated ability to suppress the proliferation of autologous stimulated dPBMC, nevertheless, priming of dAT-MSC with IFN-ɤ, might improve such defect. The results suggest that T2D might affect the immunosuppressive potential of AT-MSC and pre-conditioning of dAT-MSC with a pro-inflammatory stimulus could enhance their therapeutic effect.

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Section: Discussionmentioning

confidence: 99%

Immunomodulatory Properties of Human Adipose Mesenchymal Stromal/Stem Cell in Type 2 Diabetes Milieu.

Elshahat

Abu-Shahba²,

El-Din³

et al. 2023

Azhar International Journal of Pharmaceutical and Medical Scien

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“…Coculture of macrophages and Jurkat cells induced simultaneous in ammatory and anti-in ammatory states. The concentration of cells for coculture has been set by our previous study as Jurkat cells 2X10 6 cells/mL, and diffrentated THP-1 cells 1X10 4 cells/mL, which resulted in the same decrease in T cells in coculture in other studies [28]. In order to determine the time of hypoxia in coculture, cell viability (MTT), IL-2 and MIF at various times were determined to be 30 minutes of statistical signi cance.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Oxygen and Pentoxifylline in Hypoxic Condition

Cho

Choi

Park

et al. 2020

Preprint

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Background: Among major trauma patients in the emergency department (ED), the leading cause of morbidity and mortality is a hemorrhagic shock. The low oxygen flow with hypovolemia in trauma patients is believed to play a significant role. Hence, oxygen supply is essential in severe trauma patients with massive hemorrhage. This study aimed to investigate the effect of different oxygen environments (hypoxia 1%, normoxia 20%, hyperoxia 80% oxygen) and variable treatments such as pentoxifylline (PTX), glycerol, hypertonic saline (HTS), protease inhibitor and dexamethasone (DEXA) in macrophage and T cells. Methods: Nitric oxide synthase (iNOS) and macrophage migration inhibitory factor (MIF) were measured for macrophage. MIF, interleukin (IL)-2 and 8 were measured for T cells. MTT assay was done for measuring T cell viability. Coculture was done on T cells on top of macrophages and the same protocols were carried out. Results: PTX decreased iNOS expression mostly followed by Glycerol under hypoxia. Under the hyperoxia, PTX and other treatments decreased iNOS expressions. MIF expression was lowered with PTX under hypoxia. PTX, glycerol, HTS, and protease inhibitor were effective under hyperoxia. PTX increased T cell survival under hypoxia. Under the hyperoxia, IL-2 expressions were upregulated with PTX, Glycerol, and HTS. PTX and other treatments were effective for IL-8, too. Our results indicate that PTX, HTS, and other medications with oxygen showed an effect on macrophage and T cells under various insults and stimulations. Conclusion: Our study demonstrated potential usefulness in improving immune systems during severe inflammatory conditions similar to septic shock possibly caused by massive hemorrhage.

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“…In demonstrating the effects of hypoxia on mitogen-stimulated T cells, the authors noticed that oxygen depletion reduces T cell activation via the HLA-DR expression, inhibits T cell proliferation, and reduces pro-inflammatory, but upregulates anti-inflammatory, cytokine secretion. Mechanistically, there was increased expression of PD-1, FOXP3 (forkhead box P3), and TGFβ1, key players in the tumor immune evasion response, while genes involved in the inflammatory response, such as IL2 and interferon (IFN)γ, were downregulated [ 104 ]. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), also known as CD152, is a protein receptor that functions as an immune checkpoint and downregulates immune responses.…”

Section: Immune Cell Evasionmentioning

confidence: 99%

Hypoxia-Regulated Tumor-Derived Exosomes and Tumor Progression: A Focus on Immune Evasion

Shao

Hua

Feng

et al. 2022

IJMS

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Tumor cells express a high quantity of exosomes packaged with unique cargos under hypoxia, an important characteristic feature in solid tumors. These hypoxic tumor-derived exosomes are, crucially, involved in the interaction of cancer cells with their microenvironment, facilitating not only immune evasion, but increased cell growth and survival, enhanced angiogenesis, epithelial–mesenchymal transition (EMT), therapeutic resistance, autophagy, pre-metastasis, and metastasis. This paper explores the tumor microenvironment (TME) remodeling effects of hypoxic tumor-derived exosome towards facilitating the tumor progression process, particularly, the modulatory role of these factors on tumor cell immune evasion through suppression of immune cells, expression of surface recognition molecules, and secretion of antitumor soluble factor. Tumor-expressed exosomes educate immune effector cells, including macrophages, monocytes, T cells, natural killer (NK) cells, dendritic cells (DCs), γδ T lymphocytes, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), mast cells, and B cells, within the hypoxic TME through the release of factors that regulate their recruitment, phenotype, and function. Thus, both hypoxia and tumor-derived exosomes modulate immune cells, growth factors, cytokines, receptor molecules, and other soluble factors, which, together, collaborate to form the immune-suppressive milieu of the tumor environment. Exploring the contribution of exosomal cargos, such as RNAs and proteins, as indispensable players in the cross-talk within the hypoxic tumor microenvironmental provides a potential target for antitumor immunity or subverting immune evasion and enhancing tumor therapies.

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Adipose-derived stromal cell immunosuppression of T cells is enhanced under “physiological” hypoxia

Cited by 18 publications

References 39 publications

Immunomodulatory Properties of Human Adipose Mesenchymal Stromal/Stem Cell in Type 2 Diabetes Milieu.

Immunomodulatory Properties of Human Adipose Mesenchymal Stromal/Stem Cell in Type 2 Diabetes Milieu.

The Impact of Oxygen and Pentoxifylline in Hypoxic Condition

Hypoxia-Regulated Tumor-Derived Exosomes and Tumor Progression: A Focus on Immune Evasion

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