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PHLPP Signaling in Immune Cells.

Gema Lordén1, Avery J Lam2,3, Megan K Levings2,3,4

  • 1Department of Pharmacology, University of California, San Diego, La Jolla, CA, 92093, USA.

Current Topics in Microbiology and Immunology
|October 15, 2022
PubMed
Summary

Pleckstrin homology domain leucine-rich repeat protein phosphatases (PHLPP) are crucial regulators of innate and adaptive immunity. PHLPP1 modulates inflammatory signaling in macrophages, neutrophils, and T cells, impacting immune homeostasis and disease.

Keywords:
AKTChronic lymphocytic leukemiaIFNLPSMacrophagesPHLPPRegulatory T cellsTLR4

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Area of Science:

  • Immunology
  • Molecular Biology
  • Biochemistry

Background:

  • Pleckstrin homology domain leucine-rich repeat protein phosphatases (PHLPP) are Ser/Thr phosphatases with established tumor suppressor roles.
  • Emerging evidence highlights PHLPP isozymes' critical functions in regulating innate and adaptive immunity.

Purpose of the Study:

  • To review recent findings on the roles of PHLPP in inflammatory and regulatory signaling pathways.
  • To elucidate the impact of PHLPP on immune homeostasis and pathogenesis of immune-related diseases.

Main Methods:

  • Literature review of studies investigating PHLPP function in immune cells.
  • Analysis of signaling pathways regulated by PHLPP, including TLR4, IFN-γ receptor, and STAT1.
  • Examination of PHLPP's role in T cell regulation and B cell malignancies.

Main Results:

  • PHLPP1 dampens TLR4 and IFN-γ receptor signaling in macrophages.
  • Nuclear PHLPP1 inhibits STAT1-mediated inflammatory gene expression.
  • PHLPP1 regulates neutrophil migration and inflammation, and is essential for regulatory T cell function and B-cell leukemia apoptosis.

Conclusions:

  • PHLPP1 plays a multifaceted role in immune regulation, affecting both innate and adaptive immune responses.
  • PHLPP1 expression dynamics influence inflammatory conditions like inflammatory bowel disease and septic shock.
  • PHLPP is a key target for understanding and potentially manipulating immune responses in various diseases.