Personalized and Precision Medicine Journal
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The Multifaceted Role of CD154 in SLE: Pathogenesis, Receptor Interactions, and Emerging Therapies

Articles in Press

Document Type : Review Article

Authors

Farnaz Eghbalpour 1
Farnaz Eghbalpour 2

1 Golestan University of Medical Sciences

2 1. Department of Molecular Medicine, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran.

10.22034/pmj.2025.2058206.1058
Abstract
Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by immune dysregulation and multi-organ involvement. Central to its pathogenesis is the CD154/CD40 signaling axis, which orchestrates key immunological processes, including T-B cell collaboration, dendritic cell activation, and cytokine production. Recent findings have expanded the scope of CD154 beyond its classical receptor CD40, identifying integrins as alternative receptors, thus broadening its biological impact. These discoveries underline the complexity of CD154's role in SLE and its potential as a therapeutic target. First-generation CD154/CD40-targeted therapies showed promise but were hindered by thromboembolic complications. However, second-generation therapeutics, including monoclonal antibodies, small molecules, and gene-editing technologies, exhibit improved safety and efficacy profiles. This review delves into the molecular and cellular mechanisms of CD154 in SLE, explores its emerging roles through integrin interactions, and evaluates the therapeutic advancements targeting this axis. The findings highlight CD154 as a central mediator in SLE pathogenesis and a compelling target for innovative treatment strategies.

Keywords

Systemic lupus erythematosus (SLE)
CD154/CD40 signaling axis
immune dysregulation
therapeutic targets
innovative treatments

Subjects

Personalized and Precision Medicine Journal

Articles in Press, Accepted Manuscript
Available Online from 01 May 2025

  • Receive Date 18 April 2025
  • Accept Date 30 April 2025

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