Work

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

Year: 2026

Type: article

Abstract: Metabolic reprogramming of immune cells is emerging as a therapeutic strategy for autoimmune diseases. Here, we identify mesenchymal stem/stromal cell (MSC)-derived lactate as a signaling metabolite that reprograms monocyte metabolism and differentiation. GM-CSF enhanced glycolytic activity in bone marrow cells and expanded pro-inflammatory monocytes, whereas pharmacologic inhibition of glycolysis with 2-deoxy-D-glucose reversed these effects. MSC coculture suppressed glycolytic activation and redirected monocyte differentiation toward an immunosuppressive phenotype. MSCs produced lactate in a hypoxia-inducible factor 1α (HIF-1α)-dependent manner, and blocking lactate production through oxamate treatment or HIF1A knockdown attenuated the effects of MSCs on differentiating monocytes, whereas exogenous lactate recapitulated them. In experimental autoimmune uveoretinitis, intravenous administration of MSCs ameliorated the disease, but oxamate-pretreated or HIF1A-knockdown MSCs exhibited reduced efficacy. The HIF-1α-lactate axis may therefore represent a targetable pathway for optimizing MSC-based therapies and for developing lactate-centered interventions in autoimmune diseases.

Source: Cell Reports

DOI: 10.1016/j.celrep.2026.118104

Authors: Hyun Ju Lee, Jung Hwa Ko, Jin Suk Ryu, Joo Youn Oh

Institutions: Seoul National University, Seoul National University Hospital, Seoul National University Hospital Biomedical Research Institute

Language: English

Topic: Mesenchymal stem cell research

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,620