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Peer-reviewedCC BY-NCPrecision clinical medicine

KARAP deficiency alleviates intestinal mucosal barrier dysfunction by regulating mitochondrial homeostasis in macrophages.

  • Guiyuan Jin1,2,3
  • Yonghong Yang1,2,3
  • Fengqin Zhu1,2
  • Yun Chen1
  • Qingqing Zhao1
  • Guanjun Dong4
  • Yuzhong Wang3
  • Guangxi Zhou1,2
4 affiliations
  1. 1Department of Gastroenterology, Affiliated Hospital of Jining Medical University, Jining 272029, China.
  2. 2Jining Key Laboratory of Digestive Immunology, Affiliated Hospital of Jining Medical University, Jining 272029, China.
  3. 3Medical Research Center, Affiliated Hospital of Jining Medical University, Jining 272029, China.
  4. 4Jining Key Laboratory of Basic and Clinical Transformation of Autoimmune Diseases, Jining Medical University, Jining 272067, China.
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Abstract

Background

Killer cell activating receptor-associated protein (KARAP) has been implicated in the progression of various inflammatory and immune-mediated diseases, including ulcerative colitis (UC). Although macrophages play a pivotal role in UC pathogenesis, how KARAP regulates macrophage immune responses remains poorly understood.Methods

In this study, KARAP expression was assessed in peripheral blood mononuclear cells (PBMCs) and colonic tissues from patients with UC using quantitative real-time PCR and immunofluorescence. Dextran sulfate sodium (DSS)-induced colitis was established in KARAP knockout (KARAP⁻/⁻) and wild-type (WT) mice. In addition, macrophages isolated from KARAP⁻/⁻ and WT mice were cocultured with intestinal epithelial cells.Results

KARAP expression was increased in PBMCs from patients with UC and was particularly high in macrophages. In the DSS-induced colitis model, KARAP deficiency improved intestinal barrier integrity by preserving macrophage mitochondrial homeostasis. KARAP blockade also increased interleukin (IL)-10 expression, thereby further preserving intestinal mucosal barrier integrity. Mechanistically, increased IL-10 expression depended on enhanced mechanistic target of rapamycin (mTOR)/mitophagy-mediated mitochondrial homeostasis in KARAP⁻/⁻ macrophages.Conclusions

Our findings indicate that KARAP contributes to the regulation of intestinal mucosal barrier integrity by modulating macrophage mitochondrial homeostasis and IL-10 expression. Overall, these results offer new insight into the potential of KARAP as a new target for UC treatment strategies.

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Cite

BibTeXRIS
BibTeX
@article{jin2026karap,
  title = {{KARAP deficiency alleviates intestinal mucosal barrier dysfunction by regulating mitochondrial homeostasis in macrophages.}},
  author = {Guiyuan Jin and Yonghong Yang and Fengqin Zhu and Yun Chen and Qingqing Zhao and Guanjun Dong and Yuzhong Wang and Guangxi Zhou},
  journal = {Precision clinical medicine},
  year = {2026},
  month = sep,
  doi = {10.1093/pcmedi/pbag027},
  url = {https://europepmc.org/article/MED/42910264},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - KARAP deficiency alleviates intestinal mucosal barrier dysfunction by regulating mitochondrial homeostasis in macrophages.
AU  - Guiyuan Jin
AU  - Yonghong Yang
AU  - Fengqin Zhu
AU  - Yun Chen
AU  - Qingqing Zhao
AU  - Guanjun Dong
AU  - Yuzhong Wang
AU  - Guangxi Zhou
PY  - 2026
DA  - 2026/09/25
JO  - Precision clinical medicine
DO  - 10.1093/pcmedi/pbag027
UR  - https://europepmc.org/article/MED/42910264
AB  - Background  Killer cell activating receptor-associated protein (KARAP) has been implicated in the progression of various inflammatory and immune-mediated diseases, including ulcerative colitis (UC). Although macrophages play a pivotal role in UC pathogenesis, how KARAP regulates macrophage immune responses remains poorly understood.Methods  In this study, KARAP expression was assessed in peripheral blood mononuclear cells (PBMCs) and colonic tissues from patients with UC using quantitative real-time PCR and immunofluorescence. Dextran sulfate sodium (DSS)-induced colitis was established in KARAP knockout (KARAP⁻/⁻) and wild-type (WT) mice. In addition, macrophages isolated from KARAP⁻/⁻ and WT mice were cocultured with intestinal epithelial cells.Results  KARAP expression was increased in PBMCs from patients with UC and was particularly high in macrophages. In the DSS-induced colitis model, KARAP deficiency improved intestinal barrier integrity by preserving macrophage mitochondrial homeostasis. KARAP blockade also increased interleukin (IL)-10 expression, thereby further preserving intestinal mucosal barrier integrity. Mechanistically, increased IL-10 expression depended on enhanced mechanistic target of rapamycin (mTOR)/mitophagy-mediated mitochondrial homeostasis in KARAP⁻/⁻ macrophages.Conclusions  Our findings indicate that KARAP contributes to the regulation of intestinal mucosal barrier integrity by modulating macrophage mitochondrial homeostasis and IL-10 expression. Overall, these results offer new insight into the potential of KARAP as a new target for UC treatment strategies.
SN  - 2096-5303
SN  - 2516-1571
ER  -