Adoptive Transfers of CD4+CD25+ Tregs Raise Foxp3 Expression and Alleviate Mouse Enteritis.
Kai WangTongjia ZhuHaijun WangJinxin YangShuaishuai DuGuoying DongZhihua PeiGui-Xue HuPublished in: BioMed research international (2018)
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.
Keyphrases
- regulatory t cells
- induced apoptosis
- transcription factor
- cell cycle arrest
- signaling pathway
- immune response
- disease activity
- rheumatoid arthritis
- lymph node
- flow cytometry
- epithelial mesenchymal transition
- poor prognosis
- systemic lupus erythematosus
- south africa
- gene expression
- endoplasmic reticulum stress
- dendritic cells
- binding protein
- long non coding rna
- transforming growth factor
- skeletal muscle
- juvenile idiopathic arthritis
- metabolic syndrome
- ankylosing spondylitis
- sentinel lymph node
- heat shock protein