Journal
CELL REPORTS
Volume 25, Issue 7, Pages 1800-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2018.10.057
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Funding
- Japan Society for the Promotion of Science [16K19196, 18K11077, 26860512, 25893162, 18H07417, 15H04764, 24590387, 17H01550, 25253041]
- Clinical Research Promotion Foundation
- Takeda Science Foundation
- Leading Advanced Projects for Medical Innovation (LEAP) from the Japan Agency for Medical Research and Development (AMED) [JP18gm0010001]
- Grants-in-Aid for Scientific Research [17H01550, 26860512, 16K19196, 24590387, 25893162, 15H04764, 25253041, 18K11077] Funding Source: KAKEN
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Dendritic cell (DC) maturation induced by Toll-like receptor agonists requires activation of downstream signal transduction and metabolic changes. The endogenous metabolite citrate has recently emerged as a modulator of DC activation. However, the metabolic requirements that support citrate production remain poorly defined. Here, we demonstrate that p32/C1qbp, which functions as a multifunctional chaperone protein in mitochondria, supports mitochondrial metabolism and DC maturation. Metabolic analysis revealed that the citrate increase induced by lipopolysaccharide (LPS) is impaired in p32-deficient DCs. We also found that p32 interacts with dihy-drolipoamide S-acetyltransferase (E2 component of pyruvate dehydrogenase [PDH] complex) and positively regulates PDH activity in DCs. Therefore, we suggest that DC maturation is regulated by citrate production via p32-dependent PDH activity. p32-null mice administered a PDH inhibitor show decreased DC maturation and ovalbumin-specific IgG production in vivo, suggesting that p32 may serve as a therapeutic target for DC-related autoimmune diseases.
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