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View article: Glutamine synthetase deficiency enhances CD8 T cell survival and stress resilience in the tumor microenvironment
Glutamine synthetase deficiency enhances CD8 T cell survival and stress resilience in the tumor microenvironment Open
Cellular immunotherapy has revolutionized the treatment of hematologic malignancies yet has had limited success in the solid tumor microenvironment (TME). While insufficient nutrients can lead to T cell metabolic stress in the TME, the glu…
View article: Trsp is required by regulatory T cells to prevent lethal autoimmunity in mice
Trsp is required by regulatory T cells to prevent lethal autoimmunity in mice Open
Selenoproteins are involved in immune cell metabolism, yet the roles of these proteins in T cell development and function remain largely unknown. The Trsp gene encodes the selenocysteine tRNA (tRNASec) required for translation of all selen…
View article: Mitochondrial fatty acid synthesis and MECR regulate CD4+ T cell function and oxidative metabolism
Mitochondrial fatty acid synthesis and MECR regulate CD4+ T cell function and oxidative metabolism Open
Imbalanced effector and regulatory CD4+ T cell subsets drive many inflammatory diseases. These T cell subsets rely on distinct metabolic programs, modulation of which differentially affects T cell fate and function. Lipid metabolism is fun…
View article: Androgen signaling restricts glutaminolysis to drive sex-specific Th17 metabolism in allergic airway inflammation
Androgen signaling restricts glutaminolysis to drive sex-specific Th17 metabolism in allergic airway inflammation Open
Female individuals have an increased prevalence of many Th17 cell-mediated diseases, including asthma. Androgen signaling decreases Th17 cell-mediated airway inflammation, and Th17 cells rely on glutaminolysis. However, it remains unclear …
View article: Functional overlap of inborn errors of immunity and metabolism genes defines T cell metabolic vulnerabilities
Functional overlap of inborn errors of immunity and metabolism genes defines T cell metabolic vulnerabilities Open
Inborn errors of metabolism (IEMs) and immunity (IEIs) are Mendelian diseases in which complex phenotypes and patient rarity have limited clinical understanding. Whereas few genes have been annotated as contributing to both IEMs and IEIs, …
View article: Mitochondrial Fatty Acid Synthesis and Mecr Regulate CD4+ T Cell Function and Oxidative Metabolism
Mitochondrial Fatty Acid Synthesis and Mecr Regulate CD4+ T Cell Function and Oxidative Metabolism Open
Lipid metabolism is fundamental to CD4+ T cell metabolism yet remains poorly understood across subsets. Therefore, we performed targeted in vivo CRISPR/Cas9 screens to identify lipid-associated genes essential for T cell subset functions. …
View article: Peripheral T Cell Development and Immunophenotyping of Twins with Heterozygous <i>FOXN1</i> Mutations
Peripheral T Cell Development and Immunophenotyping of Twins with Heterozygous <i>FOXN1</i> Mutations Open
The transcription factor FOXN1 plays an established role in thymic epithelial development to mediate selection of maturing thymocytes. Patients with heterozygous loss-of-function FOXN1 variants are associated with T cell lymphopenia at bir…
View article: Tissue-Specific Dependence of Th1 Cells on the Amino Acid Transporter SLC38A1 in Inflammation
Tissue-Specific Dependence of Th1 Cells on the Amino Acid Transporter SLC38A1 in Inflammation Open
SUMMARY Amino acid (AA) uptake is essential for T cell metabolism and function, but how tissue sites and inflammation affect CD4 + T cell subset requirements for specific AA remains uncertain. Here we tested CD4 + T cell AA demands with in…
View article: Differential Effects of Glutamine Inhibition Strategies on Antitumor CD8 T Cells
Differential Effects of Glutamine Inhibition Strategies on Antitumor CD8 T Cells Open
Activated T cells undergo metabolic reprogramming to meet anabolic, differentiation, and functional demands. Glutamine supports many processes in activated T cells, and inhibition of glutamine metabolism alters T cell function in autoimmun…
View article: Overlapping Mendelian disorders of immunity and metabolism shape CD4+ T cell immunometabolism
Overlapping Mendelian disorders of immunity and metabolism shape CD4+ T cell immunometabolism Open
During the past decade it has become increasingly apparent that cellular metabolism plays a critical role in the function and regulation of the immune system. Immune cell utilization of specific metabolic pathways influences immune functio…
View article: Improving anti-tumor CD8+ T cell function through manipulating glutamine metabolism
Improving anti-tumor CD8+ T cell function through manipulating glutamine metabolism Open
Immunotherapies that bolster the anti-tumor effects of cytotoxic CD8 T lymphocytes (CTLs) have improved outcomes for many, yet most patients fail to achieve durable responses. Investigations into strategies to further enhance the cancer ki…
View article: Androgen Signaling Restricts Glutaminolysis to Drive Sex-Specific Th17 Metabolism
Androgen Signaling Restricts Glutaminolysis to Drive Sex-Specific Th17 Metabolism Open
Summary Females have increased prevalence of many Th17-mediated diseases. While androgen signaling decreases Th17-mediated inflammation, the mechanisms are not fully understood. Th17 cells rely on glutaminolysis; however, it remains unclea…
View article: Functional Overlap of Inborn Errors of Immunity and Metabolism Genes Define T Cell Immunometabolic Vulnerabilities
Functional Overlap of Inborn Errors of Immunity and Metabolism Genes Define T Cell Immunometabolic Vulnerabilities Open
SUMMARY Inborn Errors of Metabolism (IEM) and Immunity (IEI) are Mendelian diseases in which complex phenotypes and patient rarity can limit clinical annotations. Few genes are assigned to both IEM and IEI, but immunometabolic demands sugg…
View article: Subset-specific mitochondrial and DNA damage shapes T cell responses to fever and inflammation
Subset-specific mitochondrial and DNA damage shapes T cell responses to fever and inflammation Open
Heat is a cardinal feature of inflammation. Despite temperature variability and dependence of enzymes and complexes, how heat and fever affect immune cells remains uncertain. We found that heat broadly increased inflammatory activity of CD…