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Updated: Jun 10, 2026
08:37
Induction of Murine Intestinal Inflammation by Adoptive Transfer of Effector CD4+CD45RBhigh T Cells into Immunodeficient Mice
Published on: April 21, 2015
PRAS40-driven pro-inflammatory macrophage polarization is required for inflammatory bowel disease
Chengfei Zhang1, Yufei Bo1, Jia Deng1
1Department of Pathophysiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, P. R. China.
Cell Death & Disease
|June 8, 2026
Summary
Proline-rich Akt substrate of 40kDa (PRAS40) drives inflammatory bowel disease (IBD) by promoting macrophage inflammation. Targeting the PRAS40/SP1/SLC7A5 axis offers a potential therapeutic strategy for IBD.
Area of Science:
- Immunology
- Molecular Biology
- Gastroenterology
Background:
- Inflammatory bowel diseases (IBD) are chronic conditions with unknown causes and few treatments.
- Macrophage dysfunction is key in IBD, but its metabolic regulation is unclear.
- The role of PRAS40 in IBD is unknown, despite its link to colon cancer.
Purpose of the Study:
- Investigate the role of PRAS40 in IBD pathogenesis.
- Determine how PRAS40 influences macrophage function and polarization in IBD.
- Explore the PRAS40/SP1/SLC7A5 axis as a therapeutic target for IBD.
Main Methods:
- Analyzed PRAS40 expression in IBD patients and mouse models.
- Utilized global and myeloid-specific PRAS40 knockout mice.
- Performed metabolomic analysis on bone marrow-derived macrophages (BMDMs).
- Investigated signaling pathways including ERK, JNK, and mTOR.
Main Results:
- PRAS40 expression is increased in IBD patients and models.
- PRAS40 deficiency alleviates IBD symptoms, dependent on macrophages.
- PRAS40 promotes pro-inflammatory macrophage polarization via leucine and tryptophan uptake.
- The PRAS40/SP1/SLC7A5 axis enhances amino acid uptake and activates mTOR signaling.
Conclusions:
- The PRAS40/SP1/SLC7A5 axis drives macrophage pro-inflammatory polarization in IBD.
- This axis exacerbates IBD by increasing leucine and tryptophan uptake.
- Targeting this axis presents a novel therapeutic strategy for IBD.
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