Thalidomide Attenuates Colitis and Is Associated with the Suppression of M1 Macrophage Polarization by Targeting the Transcription Factor IRF5

Lu, Jiaxi; Liu, Deliang; Tan, Yuyong; Li, Rong; Wang, Xuehong; Deng, Feihong

doi:10.1007/s10620-021-07067-2

Cited by 9 publications

(5 citation statements)

References 37 publications

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“…Studies have reported a correlation between IRF5 and UC. In a clinical trial investigating thalidomide’s efficacy in treating UC, it was found that thalidomide effectively modulated M1 macrophage polarization by targeting IRF5, ultimately leading to an amelioration of inflammation ( 76 ). Yang et al.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory bowel disease and rheumatoid arthritis share a common genetic structure

Cao,

Luo,

et al. 2024

Front. Immunol.

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BackgroundThe comorbidity rate of inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) is high; nevertheless, the reasons behind this high rate remain unclear. Their similar genetic makeup probably contributes to this comorbidity.MethodsBased on data obtained from the genome-wide association study of IBD and RA, we first assessed an overall genetic association by performing the linkage disequilibrium score regression (LDSC) analysis. Further, a local correlation analysis was performed by estimating the heritability in summary statistics. Next, the causality between the two diseases was analyzed by two-sample Mendelian randomization (MR). A genetic overlap was analyzed by the conditional/conjoint false discovery rate (cond/conjFDR) method.LDSC with specific expression of gene analysis was performed to identify related tissues between the two diseases. Finally, GWAS multi-trait analysis (MTAG) was also carried out.ResultsIBD and RA are correlated at the genomic level, both overall and locally. The MR results suggested that IBD induced RA. We identified 20 shared loci between IBD and RA on the basis of a conjFDR of <0.01. Additionally, we identified two tissues, namely spleen and small intestine terminal ileum, which were commonly associated with both IBD and RA.ConclusionHerein, we proved the presence of a polygenic overlap between the genetic makeup of IBD and RA and provided new insights into the genetic architecture and mechanisms underlying the high comorbidity between these two diseases.

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Section: Discussionmentioning

confidence: 99%

Inflammatory bowel disease and rheumatoid arthritis share a common genetic structure

Cao,

Luo,

et al. 2024

Front. Immunol.

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“…Immunoreactive scores (IRSs) were applied for IHC assessment as previously described. 19 Immunoreactivity was evaluated by immunoreactive scores [IRSs] according to positive area of the cell population in the biopsy specimen staining [<25%=1; 25–50%=2; 50–75%=3; >75%=4] and positive degree [negative=0; mild =1; moderate=2; strong=3]. Scores for positive area and degree were multiplied, resulting in a total scoring range of 0–12.…”

Section: Methodsmentioning

confidence: 99%

YAP Activates STAT3 Signalling to Promote Colonic Epithelial Cell Proliferation in DSS-Induced Colitis and Colitis Associated Cancer

Deng¹,

Wu²,

Xu³

et al. 2022

JIR

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Background and Aims Yes-associated protein (YAP) is a key transcriptional coactivator of cell proliferation and differentiation. In this study, we sought to identify the roles of YAP in colonic epithelial regeneration and tumourigenesis. Methods Murine DSS-induced colitis and YAP overexpression models were constructed via lentiviral intraperitoneal injection. Stable YAP-overexpressing cells, protein immunoprecipitation, and ChIP were used to deeply explore the molecular mechanism. Results We found that the expression of YAP was dramatically diminished in the colonic crypts during the acute colitis phase, while YAP was strikingly enhanced to initiate tissue repair after DSS withdrawal. Overexpressing YAP in mice drastically accelerated epithelial regeneration, presenting with more intact structural integrity and reduced inflammatory cell infiltration in the mucosa. Further mechanistic studies showed that the expression of YAP in the nucleus was significantly increased by 2 h post-DSS removal, accompanied by upregulated protein levels of activated STAT3. Overexpression of YAP (YAP WT ) elevated the expression of activated STAT3 and its transcriptional targets and strengthened the proliferation and “wound healing” ability of colonic cells. However, these effects were reversed when STAT3 was silenced in YAP WT cells. Moreover, YAP could directly interact with STAT3 in the nucleus, and c-Myc and CyclinD1 were the transcriptional targets. Finally, during colitis-associated cancer (CAC), YAP WT promoted the progression of CAC, while the phosphomimetic YAP downregulated the expression of STAT3 and inhibited the development and progression of CAC. Conclusion YAP activates STAT3 signalling to facilitate mucosal regeneration after DSS-induced colitis. However, excessive YAP activation in the colonic epithelium promotes CAC development.

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“…In contrast, during the advanced stages of CAC, DHA impedes tumor growth by inducing tumor cell cycle arrest and apoptosis. And thalidomide treatment impedes M1 polarization within the inflammatory microenvironment, reduces DSS-induced colonic inflammation, facilitates mucosal healing, and curtails the progression of CAC ( 39 ).…”

Section: The Mechanisms Of Cancer Associated With Ibdmentioning

confidence: 99%

Overcoming cancer risk in inflammatory bowel disease: new insights into preventive strategies and pathogenesis mechanisms including interactions of immune cells, cancer signaling pathways, and gut microbiota

Zhang,

Shi,

Lin

et al. 2024

Front. Immunol.

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Inflammatory bowel disease (IBD), characterized primarily by gastrointestinal inflammation, predominantly manifests as Crohn’s disease (CD) and ulcerative colitis (UC). It is acknowledged that Inflammation plays a significant role in cancer development and patients with IBD have an increased risk of various cancers. The progression from inflammation to carcinogenesis in IBD is a result of the interplay between immune cells, gut microbiota, and carcinogenic signaling pathways in epithelial cells. Long-term chronic inflammation can lead to the accumulation of mutations in epithelial cells and the abnormal activation of carcinogenic signaling pathways. Furthermore, Immune cells play a pivotal role in both the acute and chronic phases of IBD, contributing to the transformation from inflammation to tumorigenesis. And patients with IBD frequently exhibit dysbiosis of the intestinal microbiome. Disruption of the gut microbiota and subsequent immune dysregulation are central to the pathogenesis of both IBD and colitis associated colorectal cancer (CAC). The proactive management of inflammation combined with regular endoscopic and tumor screenings represents the most direct and effective strategy to prevent the IBD-associated cancer.

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Thalidomide Attenuates Colitis and Is Associated with the Suppression of M1 Macrophage Polarization by Targeting the Transcription Factor IRF5

Cited by 9 publications

References 37 publications

Inflammatory bowel disease and rheumatoid arthritis share a common genetic structure

Inflammatory bowel disease and rheumatoid arthritis share a common genetic structure

YAP Activates STAT3 Signalling to Promote Colonic Epithelial Cell Proliferation in DSS-Induced Colitis and Colitis Associated Cancer

Overcoming cancer risk in inflammatory bowel disease: new insights into preventive strategies and pathogenesis mechanisms including interactions of immune cells, cancer signaling pathways, and gut microbiota

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