Abstract
Intestinal homeostasis requires a balanced interaction between the host innate immune system and the gut microbiota. A dysregulation of this interdependency can result in inflammatory bowel diseases (IBDs), and this dysregulation is a key pathogenic factor during the development of colorectal cancer. CARD9 is a central signaling molecule in the innate immune system, which is essential for host defense against infection. Moreover, polymorphisms in CARD9 are key risk factors for IBD development, indicating that CARD9 signaling is critical for intestinal immune homeostasis. This review summarizes recent insights into the regulation of CARD9 signaling, its pathophysiological role during IBD development via effects on the microbiota and epithelial regeneration and the pro- and antitumor immune functions of CARD9 during intestinal carcinogenesis.
Highlights
Homeostasis in the gastrointestinal tract depends on balanced interactions between the host immune system and the gut microbiome
These findings indicate that CARD9S12N deviates physiological CARD9 signaling and suggest that the respective single-nucleotide polymorphisms (SNPs) in human inflammatory bowel diseases (IBDs) could potentially contribute to intestinal inflammation through related mechanisms, this possibility remains to be investigated
In IBD, both risk-promoting and protective CARD9 variants have been identified, and based on an understanding of the protective CARD9 variant, which is defective in the CARD9TRIM62 interaction, small-molecule inhibitors that block the CARD9-TRIM62 interaction have been developed that might be useful for IBD treatment [47]
Summary
Signaling in Intestinal Immune Homeostasis and Oncogenesis. Intestinal homeostasis requires a balanced interaction between the host innate immune system and the gut microbiota. A dysregulation of this interdependency can result in inflammatory bowel diseases (IBDs), and this dysregulation is a key pathogenic factor during the development of colorectal cancer. CARD9 is a central signaling molecule in the innate immune system, which is essential for host defense against infection. Polymorphisms in CARD9 are key risk factors for IBD development, indicating that. CARD9 signaling is critical for intestinal immune homeostasis. This review summarizes recent insights into the regulation of CARD9 signaling, its pathophysiological role during. IBD development via effects on the microbiota and epithelial regeneration and the pro- and antitumor immune functions of CARD9 during intestinal carcinogenesis
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