Related Experiment Video
Updated: May 5, 2026
An IL-8 Transiently Transgenized Mouse Model for the In Vivo Long-term Monitoring of Inflammatory Responses
Published on: July 7, 2017
Regulation of IL-4 receptor signaling by STUB1 in lung inflammation
Qin Wei1, Youbao Sha, Abhisek Bhattacharya
11 Department of Medicine, Baylor College of Medicine, Houston, Texas; and.
Rationale:
IL-4Rα, the common receptor component for IL-4 and IL-13, plays a critical role in IL-4- and IL-13-mediated signaling pathways that regulate airway inflammation and remodeling. However, the regulatory mechanisms underlying IL-4Rα turnover and its signal termination remain elusive.
Objectives:
To evaluate the role of STUB1 (STIP1 homology and U-Box containing protein 1) in regulating IL-4R signaling in airway inflammation.
Methods:
The roles of STUB1 in IL-4Rα degradation and its signaling were investigated by immunoblot, immunoprecipitation, and flow cytometry. The involvement of STUB1 in airway inflammation was determined in vivo by measuring lung inflammatory cells infiltration, mucus production, serum lgE levels, and alveolar macrophage M2 activation in STUB1(-/-) mice. STUB1 expression was evaluated in airway epithelium of patients with asthma and lung tissues of subjects with chronic obstructive pulmonary disease.
Measurements And Main Results:
STUB1 interacted with IL-4Rα and targeted it for ubiquitination-mediated proteasomal degradation, terminating IL-4 or IL-13 signaling. STUB1 knockout cells showed increased levels of IL-4Rα and sustained STAT6 activation, whereas STUB1 overexpression reduced IL-4Rα levels. Mice deficient in STUB1 had spontaneous airway inflammation, alternative M2 activation of alveolar macrophage, and increased serum IgE. STUB1 levels were increased in airways of subjects with asthma or chronic obstructive pulmonary disease, suggesting that up-regulation of STUB1 might be an important feedback mechanism to dampen IL-4R signaling in airway inflammation.
Conclusions:
Our study identified a previously uncharacterized role for STUB1 in regulating IL-4R signaling, which might provide a new strategy for attenuating airway inflammation.
Insights
STUB1 targets IL-4Rα for degradation, resolving airway inflammation. STUB1 deficiency exacerbates inflammation, while its upregulation may be a feedback mechanism.
Area of Science:
- Immunology
- Molecular Biology
- Respiratory Medicine
Background:
- Interleukin-4 receptor alpha (IL-4Rα) is key in airway inflammation and remodeling.
- Mechanisms regulating IL-4Rα turnover and signal termination are not well understood.
Purpose of the Study:
- To investigate the role of STUB1 (STIP1 homology and U-Box containing protein 1) in IL-4R signaling.
- To explore STUB1's function in airway inflammation.
Main Methods:
- Immunoblotting, immunoprecipitation, and flow cytometry assessed STUB1's role in IL-4Rα degradation.
- In vivo studies in STUB1 knockout mice measured airway inflammation markers.
- STUB1 expression was analyzed in patient samples from asthma and COPD cases.
Main Results:
- STUB1 binds to IL-4Rα, promoting its ubiquitination and proteasomal degradation, thus terminating IL-4/IL-13 signaling.
- STUB1 deficiency led to elevated IL-4Rα, sustained STAT6 activation, spontaneous airway inflammation, M2 macrophage activation, and increased IgE.
- STUB1 levels were elevated in airways of asthma and COPD patients.
Conclusions:
- STUB1 acts as a negative regulator of IL-4R signaling by targeting IL-4Rα for degradation.
- STUB1 may offer a novel therapeutic strategy for airway inflammatory diseases.
More Related Videos
Related Concept Videos
01:20The JAK-STAT Signaling Pathway
01:24T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
01:16TGF - β Signaling Pathway
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
01:28Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...