TIM3/CEACAM1 pathway involves in myeloid-derived suppressor cells induced CD8 T cells exhaustion and bone marrow inflammatory microenvironment in myelodysplastic syndrome.

Myeloid-derived suppressor cells (MDSC) induced cellular immune deficiency and bone marrow inflammatory microenvironment play an important role in the pathogenesis and progression of myelodysplastic syndrome (MDS), but the underlying mechanism remains unclear. Here, we revealed that immune checkpoint protein TIM3 and CEACAM1 were highly demonstrated on MDSC and CD8 T cells in MDS patients. CD8 T cells were reduced in number and function and presented a exhaustion state.

1-deoxysphingolipids bind to COUP-TF to modulate lymphatic and cardiac cell development.

Identification of physiological modulators of nuclear hormone receptor (NHR) activity is paramount for understanding the link between metabolism and transcriptional networks that orchestrate development and cellular physiology. Using libraries of metabolic enzymes alongside their substrates and products, we identify 1-deoxysphingosines as modulators of the activity of NR2F1 and 2 (COUP-TFs), which are orphan NHRs that are critical for development of the nervous system, heart, veins, and lymphatic vessels. We show that these non-canonical alanine-based sphingolipids bind to the NR2F1/2 ligand-binding domains (LBDs) and modulate their transcriptional activity in cell-based assays at physiological concentrations.

Upregulated expression of leukocyte immunoglobulin-like receptor A3 in patients with severe aplastic anemia.

Severe aplastic anemia (SAA) is a rare and potentially life-threatening disease characterized by pancytopenia and bone marrow (BM) hypoplasia. In a previous study by our group, increased expression of leukocyte immunoglobulin-like receptors A (LILRA), LILRA3 in myeloid dendritic cells (mDCs) and LILRA5 in CD34 cells in SAA was detected using proteomics techniques, highlighting their potential role in disease pathogenesis. In the present study, the expression of LILRA1-6 mRNA was assessed in the BM mononuclear cells of patients with SAA using reverse transcription-quantitative (RT-q)PCR.

[Expression and Significance of IL-9 and IL-6 in Patients with BCR-ABL- MPN].

Objective: To investigate the expression of IL-9 and IL-6 in patients with BCR-ABL- bone marrow proli- ferative tumor (MPN), and to explore its role in the occurrence and development of MPN.

Methods: A total of 71 newly diagnosis MPN patients treated in Tianjin Medical University General Hospital from 2018 to 2019 were selected, including 32 patients with polycythemia vera (PV) and 22 patients with primary thrombocytosis (ET), and 17 patients with primary myelofibrosis (PMF). Then 58 patients who retestine after treatment were selected as therapy group，and 20 healthy volunteers were recruited as control group.

Myeloid-derived suppressor cell cytokine secretion as prognostic factor in myelodysplastic syndromes.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that play a critical immunosuppressive role in the tumour micro-environment. Although biological research on MDSCs has made progress, the relationship between the secretion of cytokines by MDSCs and poor prognosis is not clear, and there are no criteria to measure the functional status of MDSCs. Here, we detected the mRNA expression of IL-10, IL-12, TGF-β and TNF-α in MDSCs and the levels of these cytokines in MDSC culture supernatants of patients with myelodysplastic syndromes, and quantified the functional status of MDSCs by IL-10/IL-12 ratio and TGF-β/TNF-α ratio.

CD8 T cells exhaustion induced by myeloid-derived suppressor cells in myelodysplastic syndromes patients might be through TIM3/Gal-9 pathway.

CD8 T cells play a central role in antitumour immunity, which often exhibit 'exhaustion' in the setting of malignancy and chronic viral infection due to T cell immunoglobulin and mucin domain 3 (TIM3) and myeloid-derived suppressor cells (MDSCs). Our team previously found that overactive MDSCs and exhausted TIM3 CD8 T cells were observed in myelodysplastic syndromes (MDS) patients. However, it is not obvious whether MDSCs suppress CD8 T cells through TIM3/Gal-9 pathway.

Elevated TIM3 expression of T helper cells affects immune system in patients with myelodysplastic syndrome.

T cell immunoglobulin and mucin domain 3 (TIM3) expression is associated with immunosuppression and clinical outcomes in many diseases. However, the specific mechanism of TIM3 in immune system has not been clarified. In order to illustrate the mechanism of TIM3 in immune system, we analyzed the expression, function and regulation of TIM3 in T helper (Th)1 cells, Th2 cells, Th17 cells and regulatory T cells (Treg) through flow cytometry in patients with myelodysplastic syndrom (MDS).

[Relationship of Peripheral Blood IL-37 Expression with T Lymphocytes Subsets and NK Cells in Patients with Primary Immune Thrombocytopenia].

Objective: To study the correlation of IL-37 with T lymphocytes subsets and NK cells in ITP patients, and to explore its possible mechanisms involved in the pathogenesis of ITP.

Methods: Forty-five patients with newly diagnosed ITP(newly diagnosed group), 32 patients of complete remission (remission group) and 22 healthy persons(control group) were selected. The serum level of IL-37 in 3 groups was determined by enzyme linked immunosorbent assay (ELISA).

Abnormal changes in the quantity and function of osteoblasts cultured in patients with myelodysplastic syndrome.

Changes in bone marrow niches can lead to the occurrence of myelodysplastic syndrome (MDS). As an important part of the bone marrow niche, osteoblasts serve a key role in the progression of MDS. The present study investigated the quantity and function of osteoblasts and, through assays, detected changes in signaling pathways and the association with progression in MDS patients.

[Number and Function of Myeloid-Derived Suppressor Cells in Patients with Adult Primary Immune Thrombocytopenia].

Objective: To analyze the number of myeloid-derived suppressor cells(MDSC) and the level of prostaglandin E2(PGE2) in the bone marrow of adult ITP patients, and to explore their possible mechanisms involved in the pathogenesis of this disease.

Methods: Twenty-five patients of newly diagnosed ITP, 25 patients of complete remission group and 15 patients of control group were selected. The number of MDSC in the bone marrow between 3 groups was detect by flow cytometry (FCM).

Abnormal CD25 expression on hematopoietic cells in myelodysplastic syndromes.

Objective: To investigate the frequencies and biological characteristics of CD25 positive hematopoietic stem cells (HSC) in myelodysplastic syndromes.

Methods: The expression of CD25 on HSC in bone marrow derived from patients with untreated MDS patients, untreated AML patients and normal controls were accessed by flow cytometry (FCM). The correlation analysis was done between CD25 HSC and clinical parameters in MDS patients.

Increased TIM3+CD8+T cells in Myelodysplastic Syndrome patients displayed less perforin and granzyme B secretion and higher CD95 expression.

T cell immunoglobulin and mucin domain 3(TIM3) is a negative regulator of cellular immunity and it is highly expressed on CD8+T cells in persistent viral infection and cancer setting as report. However, how TIM3 expressed on CD8+T cells in myelodysplastic syndrome (MDS), that is a malignant disorder, has not been clarified. Here, decreased CD8+T cells, less IFN-γ secretion in CD8+T cells and increased TIM3 on CD8+T cells had been seen.

Th17 Cells Exhibit Antitumor Effects in MDS Possibly through Augmenting Functions of CD8+ T Cells.

Th17 cells are a newly found subset of distinct CD4+ Th effector cells' family and are found to play an important role in cancers. Myelodysplastic syndromes (MDS) are a common malignant hematological disease. Here, we showed that both the percentage and the function of Th17 cells were elevated in low-risk MDS while being decreased in high-risk MDS.

[Expression and Significance of HOXA9 in Patients with Myelodysplastic Syndromes].

Objective: To investigate the expression pattern of HOXA9 in myelodysplastic syndrome (MDS) patients and its relation with clinical characteristics and treatment response.

Methods: The mRNA and protein expression levels of HOXA9 in bone marrow cells from 33 cases of MDS, 12 cases of AML, 20 cases of ITP and 18 normal controls were detected by real-time guautitative PCR(RT-PCR) and flow cytometry, respectively.

Results: The percentage of HOXA9(+)/CD34(+) and HOXA9(+)/CD34(+)CD38(-) in MDS patients were significantly higher than that in control group (P<0.

[Hypomethylation and overexpression of CD70 in CD4+ T cells of the patients with immuno-related pancytopenia].

Objective: To study the expression of CD70 and the methylation level of CD70 promoter in immuno-related pancytopenia（IRP）patients, and explore the role of CD70 in the pathogenesis of IRP.

Methods: Thirty- five IRP patients and fifteen healthy donors were enrolled in this study. Peripheral blood mononuclear cells were isolated from venous blood by density gradient centrifugation, and CD4(+) T cells were isolated by immunomagnetic beads.

[Abnormal DNA methylation in CD4⁺ T cells from patients with immune related pancytopenia: a preliminary study].

Objective: To explore the global DNA methylation and the expression of regulatory genes for methylation in CD4⁺ T cells of the patients with immune related pancytopenia (IRP) and explore the role of methylation in the pathogenesis of IRP.

Methods: Thirty IRP patients (untreated, n = 15; remission, n = 15) and 15 healthy donors as controls were enrolled from December 2012 to December 2013. CD4⁺ T cells were sorted by immunomagnetic separation.

[Association between serum interleukin-17 level and abnormal cellular immunological status in patients with severe aplastic anemia].

Objective: To explore the role of interleukin-17 (IL-17) in the pathogenesis of severe aplastic anemia (SAA).

Methods: Peripheral blood samples were obtained from 40 SAA patients (25 untreated, 15 recovery) and 10 normal controls from October 2012 to October 2013. The level of IL-17 in peripheral blood was measured with cytometric bead array (CBA).

[Abnormal quantity of regulatory T cells in peripheral blood of patients with severe aplastic anemia and its clinical significance].

This study was purposed to investigate the role of regulatory T cells (Treg) in the immune unbalance for patients with acquired severe aplastic anemia (SAA). The flow cytometry was used to detect the quantity of CD4(+) CD25(+) CD127(dim) Tregs, T cell subset (CD4(+)/CD8(+) ratio), dendritic cell(DC) subset(mDC/pDC ratio) in 44 SAA patients(25 untreated patients and 19 recovery patients) and 23 normal controls. The correlation between Tregs and T cell subset, DC subset and hemogram were analyzed.

Elevated TIM3+ hematopoietic stem cells in untreated myelodysplastic syndrome displayed aberrant differentiation, overproliferation and decreased apoptosis.

TIM3, as a negative regulator of anti-tumor immunity, is highly expressed on LSCs, but not on normal HSCs. TIM3 on HSCs in MDS patients has not been clarified. Here, both the percentage of TIM3 on HSCs and the MFI of TIM3+ HSCs were higher in untreated MDS than control and were closed to AML, and excessive TIM3+ HSCs was closely related to clinical parameters: WPSS score, karyotype analysis, morphologic blasts, the number of cytopenia involving hematopoietic lineages, anemia and granulocytopenia.