Stromal-derived factor-1: The glycoprotein fueling autoimmune storms via CXCR4 and CXCR7.

The stromal cell-derived factor 1 (SDF-1, CXCL12) and its receptors, CXCR4 and CXCR7, play pivotal roles in regulating immune processes, contributing to the pathogenesis of autoimmune diseases through mechanisms such as inflammatory cell recruitment, angiogenesis, and cytokine secretion. This review discusses the structural and functional characteristics of the SDF-1/CXCR4/CXCR7 axes in various autoimmune conditions, including rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD). Interactions between SDF-1 and its receptors regulate leukocyte trafficking, neuroinflammation, and tissue remodeling, thereby influencing the progression of various diseases. Emerging therapeutic strategies targeting this axis demonstrate considerable promise. For instance, in RA, interventions such as anti-interleukin (IL)-17 antibodies, miR-23 mimics, and Qingluoyin granules attenuate SDF-1-mediated inflammation by modulating the nuclear factor kappa B (NF-kB) and phosphoinositide 3-kinase (PI3-K) signaling pathways. In MS, CXCR7 antagonists promote remyelination by altering the bioavailability of SDF-1. For SLE, CXCR4 inhibitors reduce renal inflammation, whereas in IBD, CXCR4 and IL-35-modified mesenchymal stem cells (MSCs) contribute to the restoration of mucosal tolerance. Innovative approaches, including CRISPR/Cas9-mediated gene editing and nanoparticle-based siRNA delivery systems, offer targeted modulation of this axis. Overall, these advances underscore the potential of the SDF-1/CXCR4/CXCR7 axes as a biomarker and therapeutic target, facilitating the development of novel, disease-specific treatments that aim to mitigate autoimmune pathology while maintaining immune competence. Furthermore, targeting this axis simultaneously inhibits inflammatory responses while promoting tissue repair.

• Publication year

  2025

• Venue

  International Journal of Biological Macromolecules

• Publication date

  2025-07-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.ijbiomac.2025.146374PMID 40738440
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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