Related Experiment Video
Updated: Jul 2, 2025
08:45
Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
Published on: July 17, 2020
6.2K
PTP1B phosphatase dampens iPSC-derived neutrophil motility and antimicrobial function
Morgan A Giese1,2, David A Bennin1, Taylor J Schoen1,3
1Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, 1550 Linden Dr. Madison 53706, WI, United States.
Journal of Leukocyte Biology
|February 28, 2024
Summary
Protein tyrosine phosphatase 1B (PTP1B) limits the function of neutrophils derived from human induced pluripotent stem cells (iPSCs). Removing PTP1B enhances iPSC-derived neutrophil (iNeutrophil) migration and pathogen control, offering a promising therapeutic avenue.
Area of Science:
- Immunology
- Stem Cell Biology
- Molecular Biology
Background:
- Neutrophils are crucial for fighting infections but have limitations for therapeutic use.
- Human induced pluripotent stem cells (iPSCs) offer a renewable source for neutrophil generation (iNeutrophils).
- Current iNeutrophils exhibit impaired signaling, limiting their effectiveness.
Purpose of the Study:
- To investigate the role of protein tyrosine phosphatase 1B (PTP1B) in regulating iNeutrophil function.
- To determine if PTP1B inhibition can enhance iNeutrophil antimicrobial capabilities.
Main Methods:
- Genetic deletion of PTP1B in iPSCs.
- Analysis of intracellular signaling pathways (PI3K, ERK).
- Assessment of neutrophil effector functions: F-actin polymerization, migration, phagocytosis, NETosis, and reactive oxygen species production.
- Evaluation of iNeutrophil response to Aspergillus fumigatus.
- Measurement of inflammatory factor production.
Main Results:
- PTP1B deletion enhanced PI3K and ERK signaling in iNeutrophils.
- PTP1B deficiency increased F-actin polymerization, cell migration, and phagocytosis.
- NETosis and reactive oxygen species production were reduced in PTP1B-deficient iNeutrophils.
- PTP1B-deficient neutrophils showed improved control of Aspergillus fumigatus.
- Depletion of PTP1B increased interleukin-8 production.
Conclusions:
- PTP1B acts as an inhibitor of iNeutrophil motility and effector functions.
- Targeting PTP1B can enhance the therapeutic potential of iNeutrophils.
- Modulating PTP1B activity may improve neutrophil-based immunotherapy.
