Mesenchymal stem cells (MSC) have recently been used successfully in humans to control severe graft-versus-host disease. However, the mechanisms involved in their immunomodulatory effects remain a matter of debate. Here, we show that MSC are unable to activate allogeneic T cells even in the presence of T-cell growth factors. We then found that MSC inhibit T-cell proliferation triggered either by allogeneic, mitogenic or antigen-specific stimuli. Interestingly, MSC inhibit T-cell proliferation by inducing apoptosis of activated T cells, but have no effect on resting T cells. Furthermore, we show that this apoptosis could be related to the conversion of tryptophan into kynurenine by indoleamine 2,3-dioxygenase expressed by MSC in the presence of IFNgamma. Moreover, we show that the inhibitory effect of MSC is neither abrogated nor modified during expansion in culture or after irradiation. Together, these results bring new insight to the mechanisms of immunosuppression induced by MSC and might help to develop their clinical use controlling immune-related adverse effects in humans.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/sj.leu.2403871 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mesenchymal Traits as an Intrinsic Feature of Undifferentiated Cells.
J Dev Biol
December 2024
Department of Neuroscience, Biomedicine and Movement-Sec. Anatomy and Histology, University of Verona, Via Le Grazie 8, 37134 Verona, Italy.
Since its first conceptualization over a century ago, the mesenchymal phenotype has traditionally been viewed as either a transient phase between successive epithelial stages or as a feature of cell types primarily devoted to structural support. However, recent findings in cancer research challenge this limited view, demonstrating that mesenchymal traits and hybrid mesenchymal/epithelial states can mark cancer cells with stem cell properties. By analyzing publicly available single-cell transcriptome datasets from early embryonic stages and adult tissues, this study aims to extend this concept beyond pathological contexts, suggesting that a partial or fully mesenchymal phenotype may represent the morphological expression of undifferentiated and multipotent states in both the developing embryo and adult organs.
View Article and Find Full Text PDFTumour-Associated Macrophages in Oral Squamous Cell Carcinoma.
Oral Dis
January 2025
Bahrain Defence Force Royal Medical Services, Riffa, Bahrain.
Objective: Tumour-associated macrophages (TAMs) are crucial in the progression and treatment response of oral squamous cell carcinoma (OSCC). TAMs infiltrate OSCC, adopting an M2-like phenotype that promotes tumour growth, metastasis and immune suppression. The current narrative review explored the roles of TAMs in OSCC, focusing on their impact on the tumour microenvironment, invasion, metastasis, angiogenesis, immunosuppression and potential therapeutic targeting.
View Article and Find Full Text PDFTranscription coactivator YAP1 promotes CCND1/CDK6 expression, stimulating cell proliferation in cloned cattle placentas.
Zool Res
January 2025
State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock (R2BGL), Inner Mongolia University, Hohhot, Inner Mongolia 010070, China.
Somatic cell nuclear transfer (SCNT) has been successfully employed across various mammalian species, yet cloned animals consistently exhibit low pregnancy rates, primarily due to placental abnormalities such as hyperplasia and hypertrophy. This study investigated the involvement of the Hippo signaling pathway in aberrant placental development in SCNT-induced bovine pregnancies. SCNT-derived cattle exhibited placental hypertrophy, including enlarged abdominal circumference and altered placental cotyledon morphology.
View Article and Find Full Text PDFExosomes Derived from Apelin-Pretreated Mesenchymal Stem Cells Ameliorate Sepsis-Induced Myocardial Dysfunction by Alleviating Cardiomyocyte Pyroptosis via Delivery of miR-34a-5p.
Int J Nanomedicine
January 2025
School of Medicine, South China University of Technology, Guangzhou, Guangdong, People's Republic of China.
Background: Exosomes sourced from mesenchymal stem cells (MSC-EXOs) have become a promising therapeutic tool for sepsis-induced myocardial dysfunction (SMD). Our previous study demonstrated that Apelin pretreatment enhanced the therapeutic benefit of MSCs in myocardial infarction by improving their paracrine effects. This study aimed to determine whether EXOs sourced from Apelin-pretreated MSCs (Apelin-MSC-EXOs) would have potent cardioprotective effects against SMD and elucidate the underlying mechanisms.
View Article and Find Full Text PDFTherapeutic Potential of Different Injection Methods for Bone Marrow Mesenchymal Stem Cell Transplantation in Buslfan-Induced Male Rat Infertility.
J Stem Cells Regen Med
October 2024
Mansoura University, Faculty of Science, Zoology department, Mansoura, Dakahlia, Egypt.
In recent years, bone marrow derived mesenchymal stem cells (BM-derived MSCs) have emerged as a powerful cell-based therapy for various diseases, including male infertility. Demonstrating the efficiency of BM-derived MSCs transplantation by different routes of injection to home and repair testis of busulfan-induced azoospermic rats. In the present study, rat BM-derived MSC was isolated and characterized for mesenchymal &hematopoietic markers using flow-cytometry.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!