Th22 Cells as Well as Th17 Cells Expand Differentially in Patients with Early-Stage and Late-Stage Myelodysplastic Syndrome

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.

Aberrant T Helper 17 Cells and Related Cytokines in Bone Marrow Microenvironment of Patients with Acute Myeloid Leukemia

“…Another researches in gastric cancer, uterine cervical cancer patients [27, 33] also found significantly elevated frequencies of Th17 cells in peripheral blood as well as in tumor draining lymph nodes. In blood malignant disease, our research showed that Th17 frequencies were increased in early-stage myelodysplastic syndrome (MDS) compared with the late-stage MDS or controls [34]. About the specific role of Th17 cells in peripheral blood of AML patients, the results were controversial, and so far no research was investigated in BM microenvironment of AML patients.…”

T helper cytokines in dry eye disease

“…These cells may be involved in epidermal immunity and remodeling in inflammatory skin diseases such as psoriasis, microbial infections, inflammatory and autoimmune diseases (Akdis et al, 2012; Eyerich et al, 2009; Kagami et al, 2010; Muhl et al, 2011; Qiao et al, 2011; Ryan-Payseur et al, 2011; Sanos and Diefenbach, 2013; Shao et al, 2012; Tian et al, 2013; Wolff et al, 2012; Zhang et al, 2011a). …”

The aberrant expression of microRNAs and correlations with T cell subsets in patients with immune thrombocytopenia

“…The discovery of Th17 and Th22 cells has opened up a new avenue for research into the etiology and treatment of a broad spectrum of diseases. Emerging evidence suggests that the imbalance of Th subsets contributes to the development of immune-related diseases, such as myelodysplastic syndrome (MDS) [9], ankylosing spondylitis (AS) and rheumatoid arthritis (RA) [10]. We and others have previously demonstrated that Th1, Th17 and Th22 cells were elevated, while the frequencies and/or function of Treg cells were suppressed in the peripheral blood of ITP patients[7, 8, 11], indicating a vital role of Th imbalance in the pathogenesis of ITP.…”