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Immune Checkpoints Are New Therapeutic Targets in Regulating Cardio-, and Cerebro-Vascular Diseases and CD4+Foxp3+

Ying Shao1,2, William Y Yang1, Gayani Nanayakkara3

  • 1Lemole Center for Integrated Lymphatics and Vascular Research, Department of Cardiovascular Sciences, Lewis Katz School of Medicine at Temple University, Philadelphia, PA19140, USA.

International Journal of Drug Discovery and Pharmacology
|February 10, 2025
PubMed

Insights

This review details immune checkpoints (ICPs) in cardiovascular and cerebrovascular diseases, exploring their cellular functions, regulation, and impact on immune cells like regulatory T cells (Tregs). It offers principles for developing new ICP-based therapies.

Area of Science:

  • Immunology
  • Cardiovascular Science
  • Neuroscience

Background:

  • Previous reviews on immune checkpoints (ICPs) in cardiovascular diseases (CVD) and cerebrovascular diseases are limited in scope.
  • A comprehensive analysis of ICPs' roles, regulation, and therapeutic potential in these conditions is needed.

Purpose of the Study:

  • To comprehensively review the cellular functions of ICPs in CVD and cerebrovascular diseases.
  • To analyze the regulation of ICP expression and its interaction with metabolic reprogramming.
  • To explore the role of ICPs in modulating immune cells, including regulatory T cells (Tregs), in disease pathogenesis.

Main Methods:

  • Comprehensive literature review focusing on ICPs in cardiovascular and cerebrovascular diseases.
  • Analysis of transcriptomic and posttranslational regulation of ICP expression.
  • Examination of ICP interactions with metabolic reprogramming and immune cell modulation.

Main Results:

  • Detailed discussion of 14 pairs of ICPs (e.g., CTLA-4/CD86-CD80, PD1-PDL-1, TIGIT-CD155) and their regulation of CVD pathogenesis.
  • Analysis of ICPs' roles in modulating CD4+Foxp3+ regulatory T cells (Tregs), T cells, and innate immune cells.
  • Identification of key regulatory mechanisms including tissue-specific and microenvironment-localized controls.

Conclusions:

  • ICPs play a significant role in the pathogenesis of CVDs and cerebrovascular diseases.
  • Understanding ICP regulation and function provides insights into immune cell modulation in these diseases.
  • Seven immunological principles are proposed to guide the development of novel ICP-based therapeutic strategies for CVDs and related conditions.

Keywords:
CD4+Foxp3+ regulatory T cells (Tregs)T cellscardiovascular diseasescerebrovascular diseasesimmune checkpoints (ICPs)innate immune cells

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