Regulation of Yujin Powder alcoholic extracts on ILC3s-TD IgA-colonic mucosal flora axis of DSS-induced ulcerative colitis

Abstract

The intestinal flora maintained by the immune system plays an important role in healthy colon. However, the role of ILC3s-TD IgA-colonic mucosal flora axis in ulcerative colitis (UC) and whether it could become an innovative pathway for the treatment of UC is unknown. Yujin Powder is a classic prescription for treatment of dampness-heat type intestine disease in traditional Chinese medicine and has therapeutic effects on UC. Hence, the present study aimed to investigate the regulatory mechanism of Yujin Powder alcoholic extracts (YJP-A) on UC via ILC3s-TD IgA-colonic mucosal flora axis. The UC mouse model was induced by drinking 3.5% dextran sodium sulfate (DSS), meanwhile, YJP-A was given orally for prevention. During the experiment, the clinical symptoms of mice were recorded. Then the intestinal injury and inflammatory response of mice about UC were detected after the experiment. In addition, the relevant indicators of ILC3s-TD IgA-colonic mucosal flora axis were detected. The results showed that YJP-A had good therapy effects on DSS-induced mice UC: improved the symptoms, increased body weight and the length of colon, decreased the disease activity index score, ameliorated the intestinal injury, and reduced the inflammation etc. Also, YJP-A significantly increased the ILC3s proportion and the expression level of MHC II; significantly decreased the proportion of Tfh cells and B cells and the expression levels of Bcl6, IL-4, Aicda in mesenteric lymph nodes of colon in UC mice and IgA in colon. In addition, by 16S rDNA sequencing, YJP-A could restore TD IgA targets colonic mucus flora in UC mice by decreasing the relative abundance of Mucispirillum, Lachnospiraceae and increasing the relative abundance of Allprevotella, Alistipes, and Ruminococcaceae etc. In conclusion, our results demonstrated that the ILC3s-TD IgA-colonic mucosal flora axis was disordered in UC mice. YJP-A could significantly promote the proliferation of ILC3s to inhibit Tfh responses and B cells class switching through MHC II, further to limit TD IgA responses toward colonic mucosal flora. Our findings suggested that this axis may be a novel and promising strategy to prevent UC.

IRF4 induces M1 macrophage polarization and aggravates ulcerative colitis progression by the Bcl6‐dependent STAT3 pathway

“…IRF4 can suppress the expression of Bcl6 27 . Bcl6 is aberrantly expressed in mesenteric lymph nodes of colon in UC mice 28 . In order to investigate whether IRF4 participates in the regulation of Bcl6, GST‐pull down and Co‐IP assays were performed.…”

“…27 Bcl6 is aberrantly expressed in mesenteric lymph nodes of colon in UC mice. 28 In order to investigate whether IRF4 participates in the regulation of Bcl6, GST-pull down and Co-IP assays were performed. Co-IP assay indicated that both IRF4 and Bcl6 immunoblot was observed in the input group and IP group but not the negative control IgG group (Figure 5A).…”

Bibliometric analysis of traditional Chinese medicine in the treatment of inflammatory bowel disease

“…22 On the As shown in the timeline overview in Figure 5B, the clusters that appeared during 2008-2014 and later during 2015-2023 demonstrated that with the passage of time, the hotspot of research has shifted from the earlier research on pathogenesis, clinical research on TCM for treating IBD, and research on pharmacological mechanisms of action related to the regulation of inflammatory factors through signaling pathways, adjuvant therapy research in treating IBD, to network pharmacology, research on pathogenesis related to intestinal flora, and the mechanism of action of Chinese medicine. [27][28][29][30][31] Among these clusters, #3 Jianpi Qingchang decoctin and #1 Qing-dai had a relatively long time span, indicating that the clinical research on the treatment of IBD by TCM had received extensive attention. The largest cluster was #0 Network pharmacology, which indicated that researchers had a strong interest in this topic.…”

Repairing the intestinal mucosal barrier of traditional Chinese medicine for ulcerative colitis: a review

“…The expression of IgA levels in colon further aggravated colon mucosa. Alcoholic extracts of Yujin Powder could ameliorate UC through upregulating the proportion of ILC3s and expression of MHC II, enhancing the inhibition of ILC3s on Tfh cells, further regulating IgA response and IgA targeted colonic mucosal flora ( Wen et al, 2022 ). Ran et al also demonstrated that Prunus humilis Bunge [Rosaceae; pruni semen] improved the expression of SIgA related genes and further regulated intestinal mucosal immune function.…”

“…The expression of IgA levels in colon further aggravated colon mucosa. Alcoholic extracts of Yujin Powder could ameliorate UC through upregulating the proportion of ILC3s and expression of MHC II, enhancing the inhibition of ILC3s on Tfh cells, further regulating IgA response and IgA targeted colonic mucosal flora (Wen et al, 2022)…”