Lower level of IL‑35 and its reduced inhibition in Th17 cells in patients with bone marrow mononuclear cells Coombs test‑positive hemocytopenia

Abstract

Interleukin (IL)-35 is the latest member of IL-12 family, which plays an important role in other autoimmune diseases. Bone marrow mononuclear cells Coombs test-positive hemocytopenia, also termed immunorelated hemocytopenia (IRH) is a type of autoimmune-associated diseases. The present study investigated the relationship of IL-35 in patients with IRH. A total of 43 patients with IRH and 19 normal controls were enrolled in the current study. Serum levels of IL-35 and IL-17 in peripheral blood were evaluated by ELISA. Regulatory T cells (Tregs) level was detected by flow cytometry and IL-35 subunits mRNA in Treg was determined using reverse transcription-quantitative polymerase chain reaction: Epstein-Barr virus induced 3 (EBI3) and IL-12α chain p35. Effect of IL-35 on T helper 17 cells (Th17) cells was determined by mix-culture of IL-35 with CD4+ T lymphocytes. Serum level of IL-35 was decreased in untreated patients with IRH compared with remission patients (P<0.01) and was significantly associated with clinical indexes. Frequency of IL-35 produced Tregs was lower and IL-35 subunits mRNA in CD4+CD25+ Tregs were decreased in patients with IRH compared with health controls (P<0.01). Serum level of IL-17 was increased in patients with IRH (P<0.01) and there was a negative correlation between IL-35 and IL-17 (r=−0.553; P<0.01). The production of Th17 cells and IL-17A mRNA expression were reduced (P<0.05) after mix-culture of CD4+ T lymphocytes with IL-35 compared with mix-culture of CD4+ T lymphocytes without IL-35. In conclusion, the present study revealed that IL-35 may be a monitoring indicator of IRH occurrence and progression. IL-35 level was lower and the inhibition on Th17 cells was reduced in the patients with IRH.

Interleukin-35 modulates the balance between viral specific CD4+CD25+CD127dim/- regulatory T cells and T helper 17 cells in chronic hepatitis B virus infection

“…However, Th17 cells frequency, RORγt mRNA, or IL-17 secretion by CD4 + T cells did not change notably in response to IL-35 stimulation. This was not consistent with the previous results in coxsackievirus-B3-induced myocarditis [41] and hemocytopenia [42], in which Th17 cells was strongly inhibited by delivery of IL-35. This might be partly due to the difference status of chronic and acute viral infections.…”

Atorvastatin improves bone marrow endothelial progenitor cell function from patients with immune-related hemocytopenia

“…IRH is a special type of bone marrow failure syndrome. The bone marrow microenvironment is dynamic, and is composed of growth factors and stromal cells (3)(4)(5). Endothelial progenitor cells (EPCs) are one of the important Original Article components and play a significant role in the bone marrow microenvironment.…”

“…Endothelial progenitor cells (EPCs) are one of the important Original Article components and play a significant role in the bone marrow microenvironment. Previous studies have shown that EPCs regulate the transport and homing of hematopoietic stem cells (4,5), and are related to the delayed recovery of hematopoietic stem cells after transplantation (6)(7)(8). Moreover, the number and function of EPCs in patients with poor chimeric function after transplantation are significantly different from those with good chimeric function, and atorvastatin can improve this difference (9).…”

Th9 Cells in Peripheral Blood Increased in Patients with Immune-Related Pancytopenia

“…The proportion balance of Th1/Th2 cells shifted to the Th2 direction [11]. The quantity and function of Th17 cells, which was named follicular helper T cells, increased [12][13][14], while Tregs and NK cells decreased in the IRP patients [14,15]. The proportion balance of pDC/mDC cells shifted to the pDC direction [16].…”