HIF-1α-driven lactate from mesenchymal stem/stromal cells reprograms monocyte metabolism and suppresses autoimmune uveoretinitis.

HIF-1α-driven lactate from mesenchymal stem/stromal cells reprograms monocyte metabolism and suppresses autoimmune uveoretinitis, highlighting a key therapeutic pathway.

• Why it matters: Autoimmune diseases often involve immune cell metabolic dysregulation, and targeting these pathways could improve treatment outcomes. Understanding how MSCs modulate immune responses via metabolism offers new therapeutic avenues.
• What they did: The study used coculture systems, pharmacologic inhibitors, and genetic knockdowns to show that MSC-derived lactate, produced in a HIF-1α-dependent manner, reprograms monocyte differentiation and reduces inflammation in autoimmune uveoretinitis.
• The result: Blocking lactate production diminished MSC efficacy, while exogenous lactate mimicked their effects, suggesting that targeting the HIF-1α-lactate axis could enhance MSC therapies and develop lactate-based treatments for autoimmune conditions.