Related Experiment Video
Updated: Jun 11, 2026
08:35
Qualitative and Quantitative Analysis of the Immune Synapse in the Human System Using Imaging Flow Cytometry
Published on: January 7, 2019
PTPN22 regulates T cell synapse formation through PSTPIP1-dependent actin remodeling
Megan D Joseph1, Cecilia Zaza1, Olivia P L Dalby1,2
1London Centre for Nanotechnology, University College London, WC1H 0AH London, UK.
Science Signaling
|June 9, 2026
Summary
Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) regulates T cell activation by interacting with PSTPIP1 to control cytoskeletal dynamics. Its deficiency causes aberrant actin remodeling and enhanced signaling, offering insights into autoimmune diseases.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) is a critical negative regulator of T cell activation and immune tolerance.
- The autoimmune disease-associated R620W variant of PTPN22 suggests its role in T cell responses.
- Understanding PTPN22's function is crucial for insights into immune dysregulation and autoimmune diseases.
Purpose of the Study:
- To investigate the role of PTPN22 in modulating T cell activation and cytoskeletal dynamics.
- To elucidate the interaction between PTPN22 and proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) in T cell signaling.
- To explore the impact of PTPN22 deficiency on actin remodeling and T cell receptor (TCR) signaling.
Main Methods:
- Utilized Jurkat cell models to study T cell activation.
- Investigated the interaction between PTPN22 and PSTPIP1 at the immunological synapse.
- Employed super-resolution DNA-PAINT to analyze nanoscale protein organization and TCR clustering.
- Assessed actin remodeling and calcium signaling in response to TCR stimulation.
Main Results:
- PTPN22 modulates cytoskeletal dynamics at the immunological synapse via interaction with PSTPIP1.
- PTPN22 deficiency disrupts Arp2/3-dependent actin remodeling, leading to excessive F-actin foci and PSTPIP1 mislocalization.
- Loss of PTPN22 enhances calcium signaling, particularly under low-affinity TCR stimulation.
- Super-resolution analysis revealed aberrant PSTPIP1-TCR colocalization and increased TCR clustering in PTPN22-deficient cells.
Conclusions:
- A novel PTPN22-PSTPIP1 signaling axis is identified, critical for regulating cytoskeletal remodeling and receptor organization in T cells.
- PTPN22 plays a key role in maintaining T cell homeostasis by controlling actin dynamics and TCR signaling.
- Dysregulation of this PTPN22-PSTPIP1 pathway may contribute to T cell hyperactivation and autoimmune diseases.
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