CARD9 Signaling in Intestinal Immune Homeostasis and Oncogenesis

Front Immunol. 2019 Mar 11:10:419. doi: 10.3389/fimmu.2019.00419. eCollection 2019.

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.

Keywords: CARD9; gut microbiome; inflammatory bowel disease; intestinal carcinogenesis; intestinal immune homeostasis; intestinal inflammation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • CARD Signaling Adaptor Proteins / genetics
  • CARD Signaling Adaptor Proteins / metabolism*
  • Carcinogenesis / immunology
  • Carcinogenesis / metabolism*
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / metabolism
  • Gastrointestinal Microbiome / genetics
  • Gastrointestinal Microbiome / immunology
  • Homeostasis / immunology*
  • Humans
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / metabolism
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Mice
  • Polymorphism, Single Nucleotide / genetics

Substances

  • CARD Signaling Adaptor Proteins
  • CARD9 protein, human
  • Card9 protein, mouse