Abstract
BackgroundImmunological mechanisms are increasingly recognized in the progression of myelodysplastic syndrome (MDS). Early-stage MDS (E-MDS) is characterized by autoimmune-mediated myelosuppression whereas late-stage MDS (L-MDS) involves immune evasion, giving dysplastic cells growth potential to progress into acute myeloid leukemia. T-helper (Th) 22 is involved in the pathogenesis of inflammatory autoimmunity and tumorigenesis. The roles of Th22 cells in the pathophysiology of E-MDS and L-MDS remain unsettled.Design and MethodsWe studied 37 MDS patients (E-MDS, n = 17; L-MDS, n = 20) and 20 healthy controls to characterize their peripheral blood (PB), as well as 25 MDS patients and 10 healthy controls to characterize their bone marrow(BM). The expression of Interleukin-22 (IL-22), IL-17 or interferon gamma (IFN-γ) was examined in E-MDS, L-MDS patients and controls by flow cytometry. The mRNA expression levels of RAR-related orphan receptor C (RORC), IL-6, tumor necrosis factor alpha (TNF-α) and IL-23 in peripheral blood mononuclear cells (PBMCs) were determined by real-time quantitative polymerase chain reaction. The levels of IL-22 and IL-17 both in PB and BM plasma were examined by enzyme-linked immunosorbent assay.ResultsIn E-MDS, peripheral Th17 cells were significantly elevated and correlated with peripheral Th22 cells compared with healthy controls and L-MDS. Significantly higher levels of peripheral Th22 expansion, mRNA expression of IL-6, TNF-α and lower level of RORC mRNA expression were observed in L-MDS compared with E-MDS. No statistical difference was found in IL-23 mRNA expression or plasma IL-22, IL-17 levels among E-MDS, L-MDS and controls.ConclusionsOur data demonstrated that L-MDS cohort had increased frequencies of peripheral Th22 cells and higher mRNA expression levels of IL-6 and TNF-α, indicating that Th22 cells along with Th17 cells or not are involved in the dynamic immune responses of MDS.
Highlights
Primary myelodysplastic syndrome (MDS) encompasses a heterogeneous group of clonal hematopoietic stem-cell disorders, characterized by ineffective hematopoiesis and an increased probability of developing acute leukemia
In Early-stage MDS (E-MDS), peripheral Th17 cells were significantly elevated and correlated with peripheral Th22 cells compared with healthy controls and L-MDS
Higher levels of peripheral Th22 expansion, mRNA expression of IL-6, tumor necrosis factor alpha (TNF-a) and lower level of receptor C (RORC) mRNA expression were observed in L-MDS compared with E-MDS
Summary
Primary myelodysplastic syndrome (MDS) encompasses a heterogeneous group of clonal hematopoietic stem-cell disorders, characterized by ineffective hematopoiesis and an increased probability of developing acute leukemia. Autoimmune-mediated myelosuppression and immune evasion of malignant clone are increasingly recognized in the process of MDS. A separate CD4+ T-cell subset was identified on the basis of cytokine interleukin(IL)-17 [4]. This subset was subsequently named T-helper cell type (Th17), expressing the lineage-specific transcription factor retinoic acid receptor-related orphan receptor C (RORC) [5]. Though Kordasti and colleagues recently showed the increased number of peripheral Th17 cells in low risk MDS [7],the mechanism of cellular immune abnormalities remains unclear. Early-stage MDS (E-MDS) is characterized by autoimmune-mediated myelosuppression whereas late-stage MDS (LMDS) involves immune evasion, giving dysplastic cells growth potential to progress into acute myeloid leukemia. The roles of Th22 cells in the pathophysiology of E-MDS and L-MDS remain unsettled
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