biostudies-literatureLiu HNational Natural Science Foundation of China929785https://www.ebi.ac.uk/biostudies/studies/S-EPMC9500237biostudies-literatureUnknown13Bcl-3 is an atypical IκB family member that regulates transcription in the nucleus by binding to the p50/p52 homologous dimer subunit. Although various studies illustrate the important role of Bcl-3 in physiological function, its role in metabolism is still unclear. We found that Bcl-3 has a metabolic regulatory effect on autoimmunity. Bcl-3-depleted mice are unable to develop experimental autoimmune encephalomyelitis. The disease resistance was linked to an increase in lactate levels in Th17 cells, and lactate could alleviate EAE development in WT mice. Bcl-3 deficient mice had more differentiated Th17 cells and an increased extracellular acidification rate in these cells. Concurrently, their ultimate respiration rate and respiratory reserve capacity were significantly lower than wild-typFrontiers in immunologyBcl-3 regulates the function of Th17 cells through raptor mediated glycolysis metabolism.PMC950023781901590Liu HYang YHuang ZZeng LGuo CHuang LWang HZhang CNiu XfalseBcl-3 regulates the function of Th17 cells through raptor mediated glycolysis metabolism.Bcl-3 is an atypical IκB family member that regulates transcription in the nucleus by binding to the p50/p52 homologous dimer subunit. Although various studies illustrate the important role of Bcl-3 in physiological function, its role in metabolism is still unclear. We found that Bcl-3 has a metabolic regulatory effect on autoimmunity. Bcl-3-depleted mice are unable to develop experimental autoimmune encephalomyelitis. The disease resistance was linked to an increase in lactate levels in Th17 cells, and lactate could alleviate EAE development in WT mice. Bcl-3 deficient mice had more differentiated Th17 cells and an increased extracellular acidification rate in these cells. Concurrently, their ultimate respiration rate and respiratory reserve capacity were significantly lower than wild-typ2022-01-01T00:00:00Z20222026-05-28T03:30:39.643Z2025-02-19T00:44:03.504ZS-EPMC95002373615977910.3389/fimmu.2022.929785