Review
The roles of macrophages in ankylosing spondylitis: from pathogenesis to therapeutic intervention target
X. Xi1, H. Pan2, H. Yuan3, J. Xu4, S. Zhao5, K. Li6, D. Li7, Y. Lu8
- School of Public Health, Gansu University of Chinese Medicine, Lanzhou, China.
- School of Public Health, Gansu University of Chinese Medicine, Lanzhou, China.
- School of Public Health, Gansu University of Chinese Medicine, Lanzhou, China.
- School of Public Health, Gansu University of Chinese Medicine, Lanzhou, China.
- School of Public Health, Gansu University of Chinese Medicine, Lanzhou, China.
- School of Public Health, Gansu University of Chinese Medicine, Lanzhou, China.
- Department of Blood Transfusion, Gansu Provincial Hospital, Lanzhou, Italy. ldh810109@126.com
- Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, China. lu73free@aliyun.com
CER19616
Review
PMID: 41930649 [PubMed]
Received: 12/12/2025
Accepted : 23/02/2026
In Press: 02/04/2026
Abstract
Ankylosing spondylitis (AS) is a chronic autoimmune disease characterised by inflammation, bone destruction and pathological new bone formation in the spine and sacroiliac joints. Macrophages, as central innate immune cells, play a pivotal role in AS pathogenesis through dynamic polarisation into pro-inflammatory M1 and anti-inflammatory M2 phenotypes. M1 macrophages dominate early disease stages, producing cytokines such as TNF-α, IL-6 and IL-1β, activating Th1/Th17 responses, and driving tissue inflammation and osteoclast-mediated bone loss. M2 macrophages prevail in later stages, secreting IL-10 and TGF-β, promoting tissue repair, angiogenesis, and ectopic bone formation, contributing to spinal ankylosis. Their plasticity is regulated by cytokine and chemokine signalling, metabolic reprogramming, genetic variants and epigenetic modifications including RNA methylation, non-coding RNAs, and histone modifications. Targeting these pathways offers promising strategies to rebalance macrophage phenotypes, reduce inflammation and prevent structural damage. This review highlights macrophages as central drivers of AS progression and discusses emerging therapeutic approaches that exploit their regulatory mechanisms for precision treatment.
