Bone Marrow-Derived Mesenchymal Stem Cells Favor the Immunosuppressive T Cells Skewing in a Helicobacter Pylori Model of Gastric Cancer

Abstract

Bone marrow-derived mesenchymal stem cells (BM-MSCs) play an important role in Helicobacter pylori-induced gastric carcinogenesis. While the mechanism is not well understood, BM-MSCs have been shown to contribute to the immunosuppressive response found in a number of diseases. Here, BM-MSCs were transplanted into the stomach of mice with a 44-week mouse-adapted H. pylori infection. At day 28 post-transplantation, BM-MSCs migrated from the subserosal to the mucosal layer of the stomach. The grafted BM-MSCs significantly stimulated systemic and local interleukin-10 (IL-10)-secreting T cell and regulatory T cell (Treg) functions. This observation was correlated with an increased percentage of CD4⁺IL-10⁺ cells and CD4⁺CD25⁺FoxP3⁺ cells in splenic mononuclear cells compared with H. pylori-infected mice not receiving BM-MSCs. Moreover, inhibitory cytokines IL-10 and transforming growth factor-β1 increased in the gastric tissue, while there was a decrease in inflammatory interferon-γ (IFN-γ). BM-MSC-transplanted mice also developed elevated IL-10/IFN-γ secreting and Treg/Th17 ratios. A coculture system in the presence or absence of BM-MSCs was also established to evaluate the immune responses in vitro. An increase in IL-10-secreting T cells and Tregs, associated with increased expression of Gata-3 and FoxP3, generation of IL-10 in the supernatant, and proliferation of gastric epithelial cells (GECs) was observed. These findings demonstrate that transplantation of BM-MSCs into a chronic H. pylori-infected mouse model results in the generation of an immunosuppressive environment. The local and systemic immunosuppression mediated by BM-MSCs likely contributed to an environment that is compatible with the development of H. pylori-induced gastric cancer.

Induction of M2 Polarization in Primary Culture Liver Macrophages from Rats with Acute Pancreatitis

“…In terms of treatment group, Liver macrophages were incubated with HBSS (control group), HBSS containing IL-4 (10 ng/ml, IL-4 group) or co-cultured with Treg cells using a transwell system (Kupffer cells: Treg cells approximately a 2∶1 ratio) as previously described [22]. Actually, we have tested different ratio (liver macrophages: Treg) at 1∶1, 2∶1 and 4∶1 before formal experiment and found 2∶1 is the most optimal ratio.…”

The Role of Probiotics in Lipopolysaccharide-Induced Autophagy in Intestinal Epithelial Cells

“…Protein preparation and western blotting were performed as previously described [25]. Briefly, cells were harvested and lysed in ice-cold RIPA lysis buffer (Beyotime, Nantong, China) for 30 min before centrifugation at 12,000 rpm for 15 minutes.…”

Culture supernatant of adipose stem cells can ameliorate allergic airway inflammation via recruitment of CD4+CD25+Foxp3 T cells

“…Lin et al observed that after transplantation of bone marrow-derived MSCs into the stomach of mice with an H. pylori infection, migration of MSC cells, from the subserosal to the mucosal layer of the stomach, was detected at 28 days posttransplantation [19]. The MSCs significantly stimulated systemic and local IL-10-secreting T cells and T reg cells [19].…”

“…The MSCs significantly stimulated systemic and local IL-10-secreting T cells and T reg cells [19]. Nemeth et al demonstrated that bone marrow-derived MSCs suppressed allergic responses in a mouse model of ragweed-induced asthma, and elicited the recruitment of T reg cells to the lung and enhanced the concentration of TGF-β in serum and in BALF [20].…”