Tier 4 — mechanistic

Exogenous α-ketoglutarate Modulates Redox Metabolism and Functions of Human Dendritic Cells, Altering Their Capacity to Polarise T Cell Response

Milanović M, Bekić M, Đokić J, Vučević D, Čolić M, Tomić S
International Journal of Biological Sciences 2024 20(3):1064-1087

Bibliography

PubMed
PMID 38322117
PubMed Central
PMC10845299
DOI
10.7150/ijbs.91109
Funding
Supported by Serbian academic research funding reported in the paper.
Competing interests
The authors reported no Ca-AKG supplement-product clinical intervention.

Study snapshot

DesignMechanistic ex-vivo/in-vitro study using human monocyte-derived dendritic cells and T-cell co-cultures.
ModelHuman monocyte-derived dendritic cells and allogeneic T cells.
SampleMultiple independent donor experiments.
InterventionNon-toxic exogenous AKG during dendritic-cell differentiation and activation.
DurationMulti-day cell differentiation and co-culture protocols.
EndpointsDendritic-cell maturation; Th1/Th2/Th17 polarization; Regulatory T cells; IL-1β; Autophagy; OXPHOS and glycolysis

What the study showed, in plain terms

This human-cell study is important because it shows that AKG is an immune modulator rather than a universally anti-inflammatory molecule.

AKG made dendritic cells more tolerogenic in several respects and reduced their ability to induce Th1 responses, but it also increased IL-1β secretion and enhanced Th17-polarizing capacity under some conditions.

These are controlled human-cell experiments, not evidence that oral Ca-AKG has the same systemic immune effects in people.

Key findings

  • AKG impaired inflammatory dendritic-cell maturation and reduced Th1 induction.
  • AKG increased regulatory/tolerogenic immune features in several assays.
  • At the same time, AKG increased IL-1β and could enhance Th17 polarization, demonstrating context-dependent immune effects.

What this study can and cannot tell us

  • In-vitro human immune-cell model.
  • AKG concentrations in culture do not map directly to oral supplement exposure.
  • Immune effects depended on cell state and stimulation context.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology