Adoptive Transfers of CD4⁺CD25⁺ Tregs Raise Foxp3 Expression and Alleviate Mouse Enteritis

Abstract

CD4+CD25+Foxp3+ Tregs control the immune response and maintain immune homeostasis. This study examined whether Tregs can affect mouse enteritis and the Foxp3 (Forkhead transcription factor) transcriptional pathway. Mouse CD4+CD25+ Treg cells were labelled using CFSE (5,6-carboxyfluorescein diacetate succinimidyl ester) and transferred to enteritis model mice. The mice were randomly divided into an enteritis group, a Treg-infusion group, a Treg-inhibiting group, and a control group. Histopathology, ELISA, flow cytometry, western blot, immunohistochemistry, and immunofluorescence were performed. Our results demonstrated that CD4+CD25+ Tregs were successfully transferred. The disease activity index (DAI) scores in the Tregs-infusion group were lower than those of the enteritis and Tregs-inhibiting groups. The number of goblet cells and inflammatory cells was reduced, and the levels of IL-1β, TNF-α, NO, and PGE2 were significantly decreased in the Tregs-infusion group compared to those in the enteritis group (p<0.05). The number of CD4+CD25+Foxp3+ Tregs and CD4+IL-17A+ Th17 cells in the mesenteric lymph nodes differed significantly from the enteritis and Tregs-inhibiting groups (p<0.05). There were more Foxp3+ Tregs and Smad3 and NFAT2 infiltrated into the duodenum after adoptive transfer of CD4+CD25+ Tregs, which was a significant difference relative to the enteritis group (p<0.05). This study demonstrated that adoptive transfer of CD4+CD25+ Tregs can decrease mouse enteritis. Foxp3 expression may be improved through the Smad3 and NFAT2 signalling pathways.

OVA-Experienced CD4+ T Cell Transfer and Chicken Protein Challenge Affect the Immune Response to OVA in a Murine Model

“…Recently, researchers have investigated the possibility of redirecting the Th2 response in favor of the Th1 response, which could reduce the occurrence of atopy [ 18 ]. Modulation of the immune response via the adoptive transfer of sensitized lymphocytes has been described previously [ 13 , 15 , 19 , 20 ]. However, the studies were mainly focused on the observation of the respiratory system.…”

“…In another study, OVA-specific Treg cells were transferred to naïve mice, resulting in suppression of the anaphylactic response to OVA [ 14 ]. Wang et al [ 15 ] demonstrated that an adoptive transfer of CD4 + CD25 + Tregs reduced the inflammatory response. Therefore, the transfer of specific Tregs may be a beneficial tool in the inhibition of immune response to OVA.…”

Cytokines secreted by arecoline activate fibroblasts that affect the balance of TH17 and Treg

“…Some studies have shown that IL‐2 is essential for the function of Treg cells. IL‐2 and TGF‐β induce the transformation of initial CD4 + T cells into CD4 + CD25 + T cells and express the forkhead transcription cytokine 3 (Foxp3) . Th17 cells are a pro‐inflammatory subpopulation that promotes autoimmune and tissue damage, while Treg cells control the balance between immune activation and tolerance .…”

Adoptive transfers of CD4+CD25+ Tregs partially alleviate mouse premature ovarian insufficiency

“…Tregs can suppress a variety of immune cells, including B, NK, NKT, CD4+, and CD8+ T cells, as well as monocytes and DCs, leading to their unique role in maintaining immune tolerance in general and controlling unwanted immune responses at various stages of autoimmunity(Bluestone, Trotta et al, 2015;Wang, Zhu, Wang, Yang, & Du, 2018). It has been well established that Tregs transplantation is a promising method in the field of autoimmune diseases.…”

“…# p < .05 and ## p < .01 compared with the pZP3 group. H & E, hematoxylin and eosin; pZP3, zona pellucida glycoprotein 3 peptide; SD, standard deviation on the potential of Tregs therapies have been conducted in a series of animal models of diseases, including enteritis, GVHD, transplantation, multiple sclerosis (MS), rheumatoid arthritis (RA), T1D, and inflammatory bowel disease, with good results(Brusko, Putnam, 2010;Cooles, Isaacs, & Anderson, 2013;Qizhi & Bluestone, 2013;Wang et al, 2018). However, there are few studies on the treatment of autoimmune POI.…”