Immune microenvironment in intervertebral disc degeneration: pathophysiology and therapeutic potential

Intervertebral disc degeneration (IDD) is a prevalent and debilitating condition that affects millions worldwide, leading to chronic back pain and a reduced quality of life. This review shifts the focus to the pivotal role of the immune microenvironment in IDD, highlighting its dual functions—exacer...

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Main Authors: Qian Ren, Ling Chen, Yibo Ma, Yansheng Huang, Sibo Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1563635/full
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author Qian Ren
Ling Chen
Yibo Ma
Yansheng Huang
Sibo Wang
author_facet Qian Ren
Ling Chen
Yibo Ma
Yansheng Huang
Sibo Wang
author_sort Qian Ren
collection DOAJ
description Intervertebral disc degeneration (IDD) is a prevalent and debilitating condition that affects millions worldwide, leading to chronic back pain and a reduced quality of life. This review shifts the focus to the pivotal role of the immune microenvironment in IDD, highlighting its dual functions—exacerbating degeneration through chronic inflammation while also offering protective mechanisms under certain conditions. Recent research highlights how immune cells such as macrophages, T cells, and B cells, along with cytokines like IL-1β, TNF-α, and IL-6, play dual roles in both exacerbating and potentially mitigating disc degeneration. Key signaling pathways, including NF-κB, MAPK, JAK-STAT, and the NLRP3 inflammasome, are discussed to illustrate their involvement in disc cell apoptosis, extracellular matrix degradation, and chronic inflammation. By synthesizing current research, this review underscores the potential of novel therapeutic strategies that target immune modulation. Anti-inflammatory drugs, biologics, stem cell therapy, and gene editing technologies are explored as promising avenues for treatment. Understanding the immune landscape of IDD not only enhances our knowledge of its pathogenesis but also opens new possibilities for effective, targeted therapies, aiming to improve patient outcomes and reduce the societal burden of this debilitating condition.
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spelling doaj-art-1dab3e9f6dae44708c880f25ccf4ac322025-08-20T02:44:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15636351563635Immune microenvironment in intervertebral disc degeneration: pathophysiology and therapeutic potentialQian Ren0Ling Chen1Yibo Ma2Yansheng Huang3Sibo Wang4Department of Joint Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi’an, Shanxi, ChinaDepartment of Spine Surgery, First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, ChinaDepartment of Urinary Surgery, Xi ‘an Jiaotong University Medical College Affiliated City Ninth Hospital, Xi’an, Shanxi, ChinaDepartment of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi’an, Shanxi, ChinaDepartment of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi’an, Shanxi, ChinaIntervertebral disc degeneration (IDD) is a prevalent and debilitating condition that affects millions worldwide, leading to chronic back pain and a reduced quality of life. This review shifts the focus to the pivotal role of the immune microenvironment in IDD, highlighting its dual functions—exacerbating degeneration through chronic inflammation while also offering protective mechanisms under certain conditions. Recent research highlights how immune cells such as macrophages, T cells, and B cells, along with cytokines like IL-1β, TNF-α, and IL-6, play dual roles in both exacerbating and potentially mitigating disc degeneration. Key signaling pathways, including NF-κB, MAPK, JAK-STAT, and the NLRP3 inflammasome, are discussed to illustrate their involvement in disc cell apoptosis, extracellular matrix degradation, and chronic inflammation. By synthesizing current research, this review underscores the potential of novel therapeutic strategies that target immune modulation. Anti-inflammatory drugs, biologics, stem cell therapy, and gene editing technologies are explored as promising avenues for treatment. Understanding the immune landscape of IDD not only enhances our knowledge of its pathogenesis but also opens new possibilities for effective, targeted therapies, aiming to improve patient outcomes and reduce the societal burden of this debilitating condition.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1563635/fullintervertebral disc degenerationimmune microenvironmentimmune modulationimmune cellstherapeutic strategies
spellingShingle Qian Ren
Ling Chen
Yibo Ma
Yansheng Huang
Sibo Wang
Immune microenvironment in intervertebral disc degeneration: pathophysiology and therapeutic potential
Frontiers in Immunology
intervertebral disc degeneration
immune microenvironment
immune modulation
immune cells
therapeutic strategies
title Immune microenvironment in intervertebral disc degeneration: pathophysiology and therapeutic potential
title_full Immune microenvironment in intervertebral disc degeneration: pathophysiology and therapeutic potential
title_fullStr Immune microenvironment in intervertebral disc degeneration: pathophysiology and therapeutic potential
title_full_unstemmed Immune microenvironment in intervertebral disc degeneration: pathophysiology and therapeutic potential
title_short Immune microenvironment in intervertebral disc degeneration: pathophysiology and therapeutic potential
title_sort immune microenvironment in intervertebral disc degeneration pathophysiology and therapeutic potential
topic intervertebral disc degeneration
immune microenvironment
immune modulation
immune cells
therapeutic strategies
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1563635/full
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AT yiboma immunemicroenvironmentinintervertebraldiscdegenerationpathophysiologyandtherapeuticpotential
AT yanshenghuang immunemicroenvironmentinintervertebraldiscdegenerationpathophysiologyandtherapeuticpotential
AT sibowang immunemicroenvironmentinintervertebraldiscdegenerationpathophysiologyandtherapeuticpotential