Improved function and balance in T cell modulation by endothelial cells in young people

Abstract

Elderly individuals exhibit unbalanced bone marrow (BM) effector T cell subset differentiation, such as increased T helper type 1 (Th1) and T cytotoxic type 1 (Tc1) cell frequencies, but the underlying mechanism is still unclear. Endothelial cells (ECs), which are instructive components of the BM microenvironment, exhibit the phenotype of semi-professional antigen-presenting cells and regulate T cell recruitment and activation. Thus, we compared the frequency and function of BM ECs, especially their capacity to regulate effector T cell subsets, between young and elderly healthy individuals, and explored the underlying mechanism of this immunomodulatory discrepancy. Although the young and elderly EC percentages were comparable, young ECs showed fewer reactive oxygen species and better migratory and tube-forming abilities than elderly ECs. Notably, increased T cell activation molecules and inflammatory cytokines were found in elderly ECs which regulated T cells to differentiate into more proinflammatory T cells, including Th1 and Tc1 cells, than young ECs.

Bone marrow macrophages are involved in the ineffective hematopoiesis of myelodysplastic syndromes

“…Differential gene expression and Gene Ontology (GO) enrichment analyses were executed by the DESeq. 2, clusterProfiler, and ggplot2 packages in R (1.16.1) (Tang et al, 2021). The MФ phenotype scores from the samples of patients were analyzed via CIBERSORTx Web site (Vallania et al, 2018; Y.‐H.…”

Dysfunctional bone marrow endothelial progenitor cells are involved in patients with myelodysplastic syndromes

“…In order to evaluate the effect of supporting ability of BM EPCs to normal HSCs, T cells or HL-60 cells, the cultivated BM EPCs from HDs or MDS or AML patients were cocultured with normal CD34 + cells, or normal CD3 + cells, or HL-60 cells [ 28 – 30 , 40 , 44 ]. HSCs or T cells were isolated from BMMNCs of HDs using CD34 or CD3 MicroBead kits (Miltenyi Biotec, Bergisch Gladbach, Germany).…”

“…After 5 days of coculture, 2 × 10 3 CD34 + cells or 2 × 10 3 HL-60 cells were plated in 24-well plates and cultured for 14 days. Colony-forming unit erythroid (CFU-E), burst-forming unit erythroid (BFU-E), colony-forming unit-granulocyte/macrophages (CFU-GM), and colony-forming unit-granulocyte, erythroid, macrophage and megakaryocyte (CFU-GEMM) measurements for CD34 + cells [ 28 , 30 , 44 ] and CFU-L measurements for HL-60 cells [ 45 ] were scored.…”