Scholarlink

<p>CARD14 is an intracellular NF-κB signaling mediator in the skin, and rare CARD14 variants have been associated with psoriasis and atopic dermatitis. CARD14 is also expressed in intestinal epithelial cells (IEC). However, its function in the intestine remains unknown. We demonstrate here that transgenic mice expressing the psoriasis-associated gain-of-function human <i>CARD14</i>(E138A) mutant specifically in IEC show mild intestinal inflammation, without epithelial damage. Moreover, <i>CARD14</i>(E138A)<sup>IEC</sup> mice show a drastic reduction in intestinal motility, often associated with rectal prolapse. Enteric neuronal survival and functionality are unaffected in <i>CARD14</i>(E138A)<sup>IEC</sup> mice. Transcriptome analysis of IEC from <i>CARD14</i>(E138A)<sup>IEC</sup> mice reveals decreased expression of antimicrobial peptides by Paneth cells, accompanied by microbial dysbiosis and increased susceptibility to enteric bacterial infection. Our findings suggest that gain-of-function CARD14 mutations may not only predispose patients to psoriasis but also mild intestinal inflammation, reduced intestinal motility, and increased sensitivity to intestinal infection. <i>CARD14</i>(E138A)<sup>IEC</sup> mice are also a valuable tool for further investigation of IEC-intrinsic molecular processes involved in intestinal inflammation and motility disorders.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

CARD14 signaling in intestinal epithelial cells induces intestinal inflammation and intestinal transit delay

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月23日

查看全文
  • Aigerim Aidarova,
  • Marieke Carels,
  • Mira Haegman,
  • Yasmine Driege,
  • Steven Timmermans,
  • Eline Van Damme,
  • Javier Aguilera-Lizarraga,
  • Maria Francesca Viola,
  • Rita de Cássia Collaço,
  • Joan Manils,
  • Steven C Ley,
  • Frank Bosmans,
  • Tom Van de Wiele,
  • Guy Boeckxstaens,
  • Claude Libert,
  • Rudi Beyaert,
  • Inna S Afonina

摘要

CARD14 is an intracellular NF-κB signaling mediator in the skin, and rare CARD14 variants have been associated with psoriasis and atopic dermatitis. CARD14 is also expressed in intestinal epithelial cells (IEC). However, its function in the intestine remains unknown. We demonstrate here that transgenic mice expressing the psoriasis-associated gain-of-function human CARD14(E138A) mutant specifically in IEC show mild intestinal inflammation, without epithelial damage. Moreover, CARD14(E138A)IEC mice show a drastic reduction in intestinal motility, often associated with rectal prolapse. Enteric neuronal survival and functionality are unaffected in CARD14(E138A)IEC mice. Transcriptome analysis of IEC from CARD14(E138A)IEC mice reveals decreased expression of antimicrobial peptides by Paneth cells, accompanied by microbial dysbiosis and increased susceptibility to enteric bacterial infection. Our findings suggest that gain-of-function CARD14 mutations may not only predispose patients to psoriasis but also mild intestinal inflammation, reduced intestinal motility, and increased sensitivity to intestinal infection. CARD14(E138A)IEC mice are also a valuable tool for further investigation of IEC-intrinsic molecular processes involved in intestinal inflammation and motility disorders.