Human dental pulp stem cells regulate allogeneic NK cells’ function via induction of anti‐inflammatory purinergic signalling in activated NK cells

Yan, Fei; Liu, Ousheng; Zhang, Haixia; Zhou, Yueying; Zhou, Di; Zhou, Zekun; He, Yuhong; Tang, Zhangui; Wang, Songlin

doi:10.1111/cpr.12595

Cited by 19 publications

(23 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Upon exposure to mesenchymal stem cells (MSCs), T cells upregulate CD39, resulting in suppression of activated T cells via increased production of extracellular adenosine (36). Similarly, studies reported that NK cells acquire the expression of CD73 after physical contact with human umbilical cord-derived MSCs or dental pulp stem cells (37,38). In cancer, NK cells from gastrointestinal stromal tumors (GISTs) have been found to express higher levels of surface CD73 (39).…”

Section: Nk Cell Signature Influences the Predictive Value Of Cd73 Gementioning

confidence: 99%

CD73 immune checkpoint defines regulatory NK cells within the tumor microenvironment

Neo¹,

Yang²,

Record³

et al. 2020

Journal of Clinical Investigation

158

133

View full text Add to dashboard Cite

We sought to investigate how peripheral blood and tumorinfiltrating NK cells differ in patients with breast cancer and sarcoma, and if tumor-infiltrating NK cells develop immunoregulatory functions. Compared with peripheral blood NK cells, tumorinfiltrating NK cells undergo phenotypic changes and acquire the expression of several immune checkpoint receptors. The expression of these immune checkpoint molecules was significantly higher on NK cells expressing CD73. Mechanistically, NK cells and IL-10 (21, 22). More recently in the context of cancer, CD56 + CD3cells in patients with ovarian cancer suppressed the growth of T cells, as observed within an ex vivo expansion of tumor-infiltrating lymphocytes (TILs). Even though it was demonstrated that the suppression was mediated by NKp46 engagement, the underlying mechanisms of how NK cells suppress are still unclear (23). It is also still unclear how conventional NK cells can undergo a phenotypic switch to suppress other TIL populations and contribute to tumor immune escape.

show abstract

Section: Nk Cell Signature Influences the Predictive Value Of Cd73 Gementioning

confidence: 99%

CD73 immune checkpoint defines regulatory NK cells within the tumor microenvironment

Neo¹,

Yang²,

Record³

et al. 2020

Journal of Clinical Investigation

158

133

View full text Add to dashboard Cite

show abstract

“…As a result, NK cells increased their ability to convert AMP into Ado 207 . Later, two further studies confirmed these findings 65,69 . Yan et al 65 showed that NK cells cocultured with the DP‐MSCs in a transwell system exhibited higher CD73 expression in comparison with the control cells.…”

Section: Adenosinergic Signaling In Immunomodulatory Effects Of Mscsmentioning

confidence: 84%

The adenosinergic pathway in mesenchymal stem cell fate and functions

Galgaro

Beckenkamp

Nunnenkamp

et al. 2021

Medicinal Research Reviews

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) play an important role in tissue homeostasis and damage repair through their ability to differentiate into cells of different tissues, trophic support, and immunomodulation. These properties made them attractive for clinical applications in regenerative medicine, immune disorders, and cell transplantation. However, despite multiple preclinical and clinical studies demonstrating beneficial effects of MSCs, their native identity and mechanisms of action remain inconclusive. Since its discovery, the CD73/ecto‐5′‐nucleotidase is known as a classic marker for MSCs, but its role goes far beyond a phenotypic characterization antigen. CD73 contributes to adenosine production, therefore, is an essential component of purinergic signaling, a pathway composed of different nucleotides and nucleosides, which concentrations are finely regulated by the ectoenzymes and receptors. Thus, purinergic signaling controls pathophysiological functions such as proliferation, migration, cell fate, and immune responses. Despite the remarkable progress already achieved in considering adenosinergic pathway as a therapeutic target in different pathologies, its role is not fully explored in the context of the therapeutic functions of MSCs. Therefore, in this review, we provide an overview of the role of CD73 and adenosine‐mediated signaling in the functions ascribed to MSCs, such as homing and proliferation, cell differentiation, and immunomodulation. Additionally, we will discuss the pathophysiological role of MSCs, via CD73 and adenosine, in different diseases, as well as in tumor development and progression. A better understanding of the adenosinergic pathway in the regulation of MSCs functions will help to provide improved therapeutic strategies applicable in regenerative medicine.

show abstract

“…The adenosinergic pathway emerges as a key mechanism by which MSCs exert hemostatic and immunomodulatory functions. Depending on the CD73/adenosine pathway, MSCs inhibited platelet activation and aggregation (Netsch et al, 2018), altered T-cell activation (Chen et al, 2016), and reduced NK cell activity (Yan et al, 2019). Of note, NK cells interacting with MSCs may acquire the expression of external nucleotide CD73.…”

Section: Regulation Of Metabolic Pathwaysmentioning

confidence: 99%

Mesenchymal Stromal Cell Immunology for Efficient and Safe Treatment of Osteoarthritis

Najar

Martel‐Pelletier

Pelletier

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Mesenchymal stem cell (MSC) therapy represents a promising approach for the treatment of osteoarthritis (OA). MSCs can be readily isolated from multiple sources and expanded ex vivo for possible clinical application. They possess a unique immunological profile and regulatory machinery that underline their therapeutic effects. They also have the capacity to sense the changes within the tissue environment to display the adequate response. Indeed, there is a close interaction between MSCs and the host cells. Accordingly, MSCs demonstrate encouraging results for a variety of diseases including OA. However, their effectiveness needs to be improved. In this review, we selected to discuss the importance of the immunological features of MSCs, including the type of transplantation and the immune and blood compatibility. It is important to consider MSC immune evasive rather than immune privileged. We also highlighted some of the actions/mechanisms that are displayed during tissue healing including the response of MSCs to injury signals, their interaction with the immune system, and the impact of their lifespan. Finally, we briefly summarized the results of clinical studies reporting on the application of MSCs for the treatment of OA. The research field of MSCs is inspiring and innovative but requires more knowledge about the immunobiological properties of these cells. A better understanding of these features will be key for developing a safe and efficient medicinal product for clinical use in OA.

show abstract

Human dental pulp stem cells regulate allogeneic NK cells’ function via induction of anti‐inflammatory purinergic signalling in activated NK cells

Cited by 19 publications

References 45 publications

CD73 immune checkpoint defines regulatory NK cells within the tumor microenvironment

CD73 immune checkpoint defines regulatory NK cells within the tumor microenvironment

The adenosinergic pathway in mesenchymal stem cell fate and functions

Mesenchymal Stromal Cell Immunology for Efficient and Safe Treatment of Osteoarthritis

Contact Info

Product

Resources

About