J Thorac Dis. 2026 May 31;18(5):535. doi: 10.21037/jtd-2026-1-0136. Epub 2026 May 22.
ABSTRACT
BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality, with smoking being its primary etiological factor. The Slit2-roundabout (Robo) signaling axis is recognized for its pivotal roles in guiding cell migration and regulating immune responses. Recently, its involvement in smoking-related lung inflammation and tissue remodeling has garnered increasing attention. The objective of this narrative review is to synthesize current evidence on the immune regulatory functions of the Slit2-Robo axis in the pathogenesis of COPD, and to explore its translational potential.
METHODS: A literature search was conducted in the PubMed and China National Knowledge Infrastructure (CNKI) databases. Search terms included "Slit2", "Robo", "chronic obstructive pulmonary disease", "inflammation", "immune cell migration", and "tissue remodeling". Publications from database inception through March 2025 were reviewed without language restrictions, with a focus on studies elucidating the mechanistic role of the Slit2-Robo signaling axis in smoking-related COPD.
KEY CONTENT AND FINDINGS: The Slit2-Robo axis is implicated in multiple processes central to COPD pathophysiology. Key findings include: (I) it modulates the recruitment, activation, and function of key immune cells (e.g., neutrophils, macrophages, lymphocytes) in the lung in response to smoke exposure. (II) It interacts with inflammatory signaling pathways, influencing the production of cytokines and chemokines that sustain chronic inflammation. (III) Beyond inflammation, this axis plays a dual role in tissue repair and remodeling, potentially affecting epithelial integrity, angiogenesis, and fibrotic processes, which are hallmarks of advanced COPD.
CONCLUSIONS: Current evidence suggests that the Slit2-Robo signaling axis may be an important regulator of immune and repair responses in smoking-induced COPD. However, the current evidence base remains limited, as most findings are derived from preclinical models and have not yet been sufficiently validated in human COPD. In addition, heterogeneity across study designs and experimental endpoints contributes to uncertainty regarding its translational significance. Further clinical and translational studies are needed to clarify its cell-specific and stage-specific roles, assess its biomarker value, and determine the feasibility of therapeutic targeting in COPD.
PMID:42306688 | PMC:PMC13266893 | DOI:10.21037/jtd-2026-1-0136