biostudies-literature00490Unknown8(11)Dong LFollicular helper T (T_FH) cells are critical for germinal center (GC) formation and are responsible for effective B cell-mediated immunity; metabolic signaling is an important regulatory mechanism for the differentiation of T_FH cells. However, the precise roles of hypoxia inducible factor (HIF) 1?-dependent glycolysis and oxidative phosphorylation (OXPHOS) metabolic signaling remain unclear in T_FH cell differentiation. Herein, we investigated the effects of glycolysis and OXPHOS on T_FH cell differentiation and GC responses using a pharmacological approach in mice under a steady immune status or an activated immune status, which can be caused by foreign antigen stimulation and viral infection. GC and T_FH cell responses are related to signals from glycolytic metabolism in mice of different ages. Foreign, specific antigen-induced GC, and T_FH cell responses and metabolic signals are essential upon PR8 infection. Glycolysis and succinate-mediated OXPHOS are required for the GC response and T_FH cell differentiation. Furthermore, HIF1? is responsible for glycolysis- and OXPHOS-induced alterations in the GC response and T_FH cell differentiation under steady or activated conditions <i>in vivo</i>. Blocking glycolysis and upregulating OXPHOS signaling significantly recovered T_FH cell differentiation upon PR8 infection and ameliorated inflammatory damage in mice. Thus, our data provide a comprehensive experimental basis for fully understanding the precise roles of HIF1?-mediated glycolysis and OXPHOS metabolic signaling in regulating the GC response and T_FH cell differentiation during stable physiological conditions or an antiviral immune response.Cellshttps://www.ebi.ac.uk/biostudies/studies/S-EPMC6912655biostudies-literatureHIF1?-Dependent Metabolic Signals Control the Differentiation of Follicular Helper T Cells.PMC6912655Li YHe YZhou SCao YDong LBi YLiu G49falseHIF1?-Dependent Metabolic Signals Control the Differentiation of Follicular Helper T Cells.Follicular helper T (T_FH) cells are critical for germinal center (GC) formation and are responsible for effective B cell-mediated immunity; metabolic signaling is an important regulatory mechanism for the differentiation of T_FH cells. However, the precise roles of hypoxia inducible factor (HIF) 1?-dependent glycolysis and oxidative phosphorylation (OXPHOS) metabolic signaling remain unclear in T_FH cell differentiation. Herein, we investigated the effects of glycolysis and OXPHOS on T_FH cell differentiation and GC responses using a pharmacological approach in mice under a steady immune status or an activated immune status, which can be caused by foreign antigen stimulation and viral infection. GC and T_FH cell responses are related to signals from glycolytic metabolism in mice of different ages. Foreign, specific antigen-induced GC, and T_FH cell responses and metabolic signals are essential upon PR8 infection. Glycolysis and succinate-mediated OXPHOS are required for the GC response and T_FH cell differentiation. Furthermore, HIF1? is responsible for glycolysis- and OXPHOS-induced alterations in the GC response and T_FH cell differentiation under steady or activated conditions <i>in vivo</i>. Blocking glycolysis and upregulating OXPHOS signaling significantly recovered T_FH cell differentiation upon PR8 infection and ameliorated inflammatory damage in mice. Thus, our data provide a comprehensive experimental basis for fully understanding the precise roles of HIF1?-mediated glycolysis and OXPHOS metabolic signaling in regulating the GC response and T_FH cell differentiation during stable physiological conditions or an antiviral immune response.2019-01-01T00:00:00Z2019 Nov2021-03-05T08:34:48Z2020-05-22T01:27:53ZS-EPMC69126553174422710.3390/cells8111450