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Pin1 Regulates IL-5 Induced Eosinophil Polarization and Migration
Zhong-Jian Shen1, Jie Hu1, Melissa A O'Neal1
1Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Cells
|January 26, 2021
Summary
The prolyl isomerase, Pin1, is crucial for eosinophil (Eos) polarization and migration. Pin1 regulates cytoskeletal changes by modulating Rho GTPase activity, offering a potential therapeutic target for reducing lung inflammation in asthma.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Eosinophils (Eos) are key inflammatory cells involved in allergic responses.
- Cytokine-induced polarization and migration are critical for Eos to reach tissues like the lungs.
- The molecular mechanisms regulating Eos shape change and migration are not fully understood.
Purpose of the Study:
- To investigate the role of the prolyl isomerase, Pin1, in eosinophil polarization and migration.
- To elucidate the molecular pathways linking Pin1 to cytoskeletal regulation in eosinophils.
Main Methods:
- Co-immunoprecipitation and immunofluorescence to study Pin1 interactions.
- Analysis of Rho GTPase activity and cofilin phosphorylation.
- Assessment of F-actin polymerization, cell polarization, and directed migration in response to cytokines (IL-5) and chemokines.
Main Results:
- Pin1 directly interacts with members of the Rho GTPase family.
- Pin1 deficiency or inhibition significantly reduces IL-5-induced Rho GTPase activity and cofilin phosphorylation.
- Reduced F-actin polymerization, cell polarization, and chemokine-directed migration were observed in Pin1-deficient or inhibited cells.
Conclusions:
- Pin1 is essential for IL-5-induced eosinophil polarization and migration.
- Pin1 regulates eosinophil cytoskeletal organization and morphology via modulation of Rho GTPase activity.
- Targeting Pin1 presents a potential therapeutic strategy to mitigate pulmonary eosinophil accumulation in asthma.
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