Regulatory Effect of Sishen Pill on Tfh Cells in Mice With Experimental Colitis

Abstract

The T follicular helper T (Tfh) cells play a significant role in the pathogenesis of inflammatory bowel disease (IBD), which is regulated by the Bcl-6/Blimp-1 pathway. Some studies have suggested that regulating activation of the Bcl-6/Blimp-1 pathway should be an effective method to treat IBD. Sishen Pill (SSP) has been used frequently to treat chronic colitis. Its mechanism is related to the downstream proteins in the Bcl-6/Blimp-1 pathway. However, it is unknown whether SSP regulates the function and differentiation of Tfh cells to treat IBD. In the present study, chronic colitis was induced by dextran sodium sulfate and treated with SSP for 7 days. SSP effectively treated chronic colitis, regulated the balance between Tfh10, Tfh17 and T follicular regulatory cells, while SSP increased the Blimp-1 level, inhibited expressions of Bcl-6, T-cell costimulator, programmed death (PD)-1 and PD-ligand 1 on the surface of Tfh cells. SSP inhibited activation of BcL-6, phosphorylated signal transducer and activator of transcription (p-STAT)3, signal lymphocyte activation molecule (SLAM)associated protein but improved Blimp-1 and STAT3 expression in colonic tissues. The results indicated that SSP regulated the differentiation and function of Tfh cells to treat IBD, which was potentially related with inhibiting the Bcl-6/Blimp-1 pathway.

Integrating Transcriptomics and Metabolomics to Explore the Novel Pathway of Fusobacterium nucleatum Invading Colon Cancer Cells

“…Upregulated genes such as DHRS2, ID2 [ 32 ], CCNA1 [ 33 ], EGR2 [ 34 ], WNT4 [ 35 ], RIPK4 [ 36 ], PDK4 [ 37 ], IL-11 [ 38 ], and MAPK4 play a role in promoting the development of colon cancer and various malignancies [ 39 ]. IL-16 plays a role in promoting cellular inflammation [ 40 ]; BCl-6 plays a role in inhibiting apoptosis in colon cancer cells [ 41 ]; and NFKBIZ plays a role in promoting the expression of the IL-17 inflammatory signaling pathway [ 42 ]. Downregulated genes, such as DMTN, play a role in inhibiting the proliferation and metastasis of colon cancer tumors [ 43 ].…”

Effect of curcumin on regulatory B cells in chronic colitis mice involving TLR/MyD88 signaling pathway

“…After curcumin treatment, it significantly restored the length of colon, reduced colon weight, colon weight index and pathological injury score. Colitis is typically characterized by inflammatory cell infiltration and increased secretion of pro‐inflammatory cytokines TNF‐α, IL‐6, IL‐33, CCL‐2, IL‐1β, TGF‐β1, and decreased secretion of anti‐inflammatory cytokines IL‐4, IL‐10, IL‐13, IgA (X. K. Liu et al, 2020; Long et al, 2022; Nijakowski et al, 2021; Uddin et al, 2022). At the same time, Curcumin reduced the proinflammatory cytokines TNF‐α, IL‐6, IL‐33, CCL‐2, IL‐1β and TGF‐β1, significantly promoted the secretion of IL‐4, IL‐10, IL‐13 and IgA, suggesting that curcumin can effectively treat colitis in mice by restoring the balance of the proinflammatory and anti‐inflammatory factors.…”

“…After curcumin treatment, it significantly restored the length of colon, reduced colon weight, colon weight index and pathological injury score. Colitis is typically characterized by inflammatory cell infiltration and increased secretion of pro-inflammatory cytokines TNF-α, IL-6, IL-33, CCL-2, IL-1β, TGF-β1, and decreased secretion of anti-inflammatory cytokines IL-4, IL-10, IL-13, IgA (X. K. Liu et al, 2020;Long et al, 2022;Nijakowski et al, 2021;Uddin et al, 2022) UC will be caused (Li et al, 2016;Ogino et al, 2021). Bone marrow the proliferation of T cells (Sanchez et al, 2020).…”

IL‐21 treatment recovers follicular helper T cells and neutralizing antibody production in respiratory syncytial virus infection

“…It is possible that the mechanism by which PD‐1–PD‐L1 interactions inhibit Tfh cells function is by downregulation of c‐Maf expression in these cells, a transcriptional factor involved in transactivation of both the promoter and enhancer of the IL‐21 gene, and is inversely associated with PD‐L1 expression 24,64 . We did not explore the capacity of RSV to induce PD‐L1 expression in Tfh cells, which have been already shown to play a role in a colitis mice model 65 . PD‐L1 upregulation in Tfh cells could be another important pathway to affect Tfh‐cell function, decreasing IL‐21 production.…”