The Study on the Regulation of Th Cells by Mesenchymal Stem Cells Through the JAK-STAT Signaling Pathway to Protect Naturally Aged Sepsis Model Rats

Abstract

Sepsis is the leading cause of death among patients, especially elderly patients, in intensive care units worldwide. In this study, we established a sepsis model using naturally aged rats and injected 5×106 umbilical cord-derived MSCs via the tail vein. Each group of rats was analyzed for survival, examined for biochemical parameters, stained for organ histology, and analyzed for the Th cell subpopulation ratio and inflammatory cytokine levels by flow cytometry. Western blotting was performed to detect the activity of the JAK-STAT signaling pathway. We designed the vitro experiments to confirm the regulatory role of MSCs, and verified the possible mechanism using JAK/STAT inhibitors. It was revealed from the experiments that the 72 h survival rate of sepsis rats treated with MSCs was significantly increased, organ damage and inflammatory infiltration were reduced, the levels of organ damage indicators were decreased, the ratios of Th1/Th2 and Th17/Treg in peripheral blood and spleen were significantly decreased, the levels of pro-inflammatory cytokines such as IL-6 were decreased, the levels of anti-inflammatory cytokines such as IL-10 were increased, and the levels of STAT1 and STAT3 phosphorylation were reduced. These results were validated in in vitro experiments. Therefore, this study confirms that MSCs can control the inflammatory response induced by sepsis by regulating Th cells and inflammatory factors, and that this leads to the reduction of tissue damage, protection of organ functions and ultimately the improvement of survival in aged sepsis model rats. Inhibition of the JAK-STAT signaling pathway was surmised that it may be an important mechanism for their action.

Screening and identification of the core immune‐related genes and immune cell infiltration in severe burns and sepsis

“…The JAK/STAT signalling pathway involving IL10 is an important therapeutic target in sepsis. Mesenchymal stem cells regulate The cells and inflammatory factors through the JAK/STAT signalling pathway to control the inflammatory response induced by sepsis, thus improving the survival rate of sepsis model rats 41 . In addition, 7‐α‐obacunyl acetate significantly improves the survival rate of septic mice by inhibiting the JAK/STAT signalling pathway 42 .…”

Effects of mammalian target of rapamycin and aryl hydrocarbon receptor‐mediating autophagy signaling on the balance of Th17/Treg cells during perinatal bisphenol A exposure in female offspring mice

“…The splenic Treg and Th17 lymphocytes were detected by flow cytometry according to previously described 17,18 . Briefly fresh spleen tissue of female offsprings was made into a single‐cell suspension.…”

“…The splenic Treg and Th17 lymphocytes were detected by flow cytometry according to previously described. 17,18 Briefly fresh spleen tissue of female offsprings was made into a single-cell suspension. The cells were stained by PerCP/Cy5.5-CD3 (0.2 mg/ml, BioLegend), FITC-CD4 (0.5 mg/mL, BioLegend), PE-CD25 (0.2 mg/ml, BioLegend), PE-IL-17 (0.2 mg/ml, BioLegend) and Alexa Fluor ® 647-Foxp3 (0.2 mg/ml, BioLegend) antibodies for 30 min without light at room temperature.…”

Research progress on the role of PKM2 in the immune response

“…Among helper T cell subsets, PKM2 acts on the Stat family in proinflammatory T cell subset differentiation. Pkm2 regulates STAT1/STAT4 to induce Th1 formation and participates in cellular immunity (20). Pkm2 can then regulate STAT6 and STAT3 phosphorylation to regulate the differentiation of Th2 1) In its dimeric form, PKM2 can translocate to the nucleus to regulate the expression of numerous proteins involved in complex biological and biochemical processes.…”