Bone marrow mesenchymal stem cells regulate the dysfunction of NK cells via the T cell immunoglobulin and ITIM domain in patients with myelodysplastic syndromes

Abstract

Abstract Background Myelodysplastic syndrome (MDS) is a clonal disease of hematopoietic cells, characterized by hematopoietic cell hematopoiesis and a high risk of transformation into acute myeloid leukemia (AML). Although the underlying mechanism is unclear, MDS is often associated with immune system disorders, especially cellular immune abnormalities. We analyzed the number of lymphocyte subsets by flow cytometry assay and explored the alteration of lymphocyte subsets in MDS. Methods Healthy controls, inpatients with primary MDS and patients with AML diagnosed from January 2017 to July 2021 were included. Flow cytometry assays were used to study lymphocyte subsets obtained from the bone marrow of the participants as well as changes in natural killer (NK) cell function. One-way analysis of variance and Student’s t-test were used to analyze the data. Results We found a reduction in the number and function of NK cells in patients with MDS. By further measuring the activating and inhibitory receptors on the surface of NK cells, we found that the T cell immunoglobulin and ITIM domain (TIGIT) was the highest expressed marker on NK cells. Additionally, the expression of CD155, which is the ligand of TIGIT, was significantly higher than expressions of CD112 and CD113 on bone marrow mesenchymal stem cells (BMSCs). Conclusions The co-culture results of BMSCs and NK cells demonstrated that BMSCs regulate NK cells through the TIGIT/CD155 interaction, indicating that NK cells play a vital role in MDS progression. BMSCs regulate the function of NK cells via TIGIT/CD155. Video Abstract

Keywords

• Myelodysplastic syndrome
• Immune system
• Natural killer cells
• Bone marrow mesenchymal stem cells
• T cell immunoglobulin and ITIM domain