Related Experiment Video
Updated: Jun 6, 2025
08:43
Adoptive Immunotherapy of iNKT Cells in Glucose-6-Phosphate Isomerase G6PI-Induced RA Mice
Published on: January 31, 2020
6.8K
IFITM1 aggravates ConA-Induced autoimmune hepatitis by promoting NKT cell activation through increased AMPK-Dependent
Jie Sun1, Haozhe Xu1, Buer Li2
1Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing 10020, China; Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
International Immunopharmacology
|November 27, 2024
Summary
Interferon-induced transmembrane 1 (IFITM1) protein is crucial for natural killer T (NKT) cell function in autoimmune hepatitis (AIH). Loss of IFITM1 reduces liver injury by improving NKT cell mitochondrial function and survival.
Area of Science:
- Immunology
- Hepatology
- Molecular Biology
Background:
- Interferon-induced transmembrane 1 (IFITM1) is recognized for its role in antiviral immunity.
- Its specific involvement in autoimmune hepatitis (AIH) pathogenesis is not well understood.
Purpose of the Study:
- To investigate the role of IFITM1 in a Concanavalin A (ConA)-induced mouse model of AIH.
- To determine the impact of IFITM1 deficiency on natural killer T (NKT) cell function and liver injury.
Main Methods:
- Utilized a ConA-induced AIH mouse model.
- Compared wild-type and IFITM1 knockout (IFITM1-/-) mice.
- Analyzed liver injury markers, inflammatory cytokine levels, and NKT cell activity.
- Employed single-cell RNA sequencing and in vivo validation of mitochondrial function and the AMPK pathway.
Main Results:
- IFITM1 expression was significantly upregulated in AIH, particularly in NKT cells.
- IFITM1-/- mice showed reduced liver injury, inflammation, and NKT cell infiltration.
- IFITM1 deficiency impaired NKT cell proliferation, cytokine production, and cytotoxicity.
- IFITM1 is essential for mitochondrial function and ATP synthesis via the AMPK pathway in NKT cells.
Conclusions:
- IFITM1 plays a critical role in regulating NKT cell activation, survival, and function during AIH.
- Targeting IFITM1 may offer a therapeutic strategy for autoimmune liver diseases.
Related Concept Videos
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
117
Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
117
01:46Electron Transport Chain: Complex I and II
11.7K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
11.7K
01:17Gastritis-II: Pathophysiology
253
Gastritis is marked by disruption of the mucosal barrier that usually protects the stomach tissue from digestive juices and manifests in acute and chronic forms.
In acute gastritis, the gastric mucosa becomes swollen and red and undergoes superficial erosion. Superficial ulceration may lead to bleeding.
In chronic gastritis, persistent or repeated insults lead to chronic inflammatory changes and, eventually, thinning or atrophy of the gastric tissue.
Gastritis can stem from various causes, each...
In acute gastritis, the gastric mucosa becomes swollen and red and undergoes superficial erosion. Superficial ulceration may lead to bleeding.
In chronic gastritis, persistent or repeated insults lead to chronic inflammatory changes and, eventually, thinning or atrophy of the gastric tissue.
Gastritis can stem from various causes, each...
253
02:26NF-κB-dependent Signaling Pathway
7.2K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.2K
01:17Intracellular Signaling Affects Focal Adhesions
2.6K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.6K
01:22PI3K/mTOR/AKT Signaling Pathway
3.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.4K