ArticleNeurospine2026
TAFA4 Mitigates Intervertebral Disc Degeneration by Modulating Macrophage Polarization and Inhibiting ROS-NLRP3 Inflammasome Activation.
Article in Neurospine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Gut-Intervertebral Disc Axis: Gut Microbiome-Driven Immune-Metabolic Imbalance and Intervertebral Disc Degeneration.Journal of cellular physiology · 2026Review
- Neuroimmune regulation of post-traumatic bone regeneration: focus on inflammatory switching and functional recovery.Frontiers in immunology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
objectiveIntervertebral disc degeneration (IVDD) is a complex pathological process involving inflammation, oxidative stress, and immune dysregulation. Emerging evidence suggests that neuroimmune interactions contribute to IVDD progression, but the role of neuropeptide-like factors remains poorly understood.
methodsWe investigated whether Gαi-interacting protein (GINIP+) sensory neurons infiltrate degenerative discs and secrete TAFA chemokine like family member 4 (TAFA4), a neuron-derived cytokine known to influence macrophage activity. In vivo and in vitro models were used to assess TAFA4 expression, its regulatory effects on macrophage polarization, reactive oxygen species (ROS) production, inflammasome activation, and disc cell phenotype. Knockdown of TAFA4 was achieved via lentiviral transduction in rabbit discs and cell coculture models.
resultsTAFA4 was upregulated in IVDD tissues and colocalized with GINIP+ neurons. Knockdown of TAFA4 in vivo exacerbated disc degeneration, increased M1 macrophage presence, elevated ROS levels, and activated the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. In vitro, GINIP+ neurons promoted macrophage M2 polarization and interleukin (IL)-10 production while suppressing tumor necrosis factor-α and IL-1β. These effects were reversed by TAFA4 knockdown. Moreover, TAFA4 attenuated ROS-dependent NLRP3 activation and preserved anabolic marker expression (ACAN [aggrecan], COL II [type II collagen], SOX9 [SRY-box transcription factor 9]), while reducing catabolic and hypertrophic-related markers (MMP13 [matrix metalloproteinase 13], ADAMTS5 [a disintegrin and metalloproteinase with thrombospondin motifs 5], COL X [collagen type X alpha 1 chain], RUNX2 [Runt-related transcription factor 2]) in nucleus pulposus cells.
conclusionTAFA4 acts as a neuron-derived mediator of neuroimmune crosstalk in IVDD that modulates macrophage polarization and oxidative stress, thereby delaying disc degeneration. This neuron-immune axis represents a potential therapeutic target.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.