Publications by authors named "I Kaymak"
Article Synopsis
- Coordination of cellular metabolism is crucial for effective CD8 T cell responses during infections, highlighting the role of cytosolic acetyl-CoA production.
- The enzyme ATP citrate lyase (ACLY) is responsible for generating acetyl-CoA from citrate, and its absence leads T cells to rely on an alternative pathway involving acyl-CoA synthetase short-chain family member 2 (ACSS2) which uses acetate.
- Both ACLY and ACSS2 are important for managing acetyl-CoA levels, impacting T cell function through modifications like histone acetylation and chromatin accessibility at key effector gene sites.
Infusion of C-labeled metabolites provides a gold standard for understanding the metabolic processes used by T cells during immune responses in vivo. Through infusion of C-labeled metabolites (glucose, glutamine, and acetate) in -infected mice, we demonstrate that CD8 T effector (Teff) cells use metabolites for specific pathways during specific phases of activation. Highly proliferative early Teff cells in vivo shunt glucose primarily toward nucleotide synthesis and leverage glutamine anaplerosis in the tricarboxylic acid (TCA) cycle to support adenosine triphosphate and de novo pyrimidine synthesis.
View Article and Find Full Text PDFInflammatory bowel disease (IBD) is an umbrella term for two conditions (Crohn's Disease and Ulcerative Colitis) that is characterized by chronic inflammation of the gastrointestinal tract. The use of pre-clinical animal models has been invaluable for the understanding of potential disease mechanisms. However, despite promising results of numerous therapeutics in mouse colitis models, many of these therapies did not show clinical benefits in patients with IBD.
View Article and Find Full Text PDFEnvironmental nutrient availability influences T cell metabolism, impacting T cell function and shaping immune outcomes. Here, we identified ketone bodies (KBs)-including β-hydroxybutyrate (βOHB) and acetoacetate (AcAc)-as essential fuels supporting CD8 T cell metabolism and effector function. βOHB directly increased CD8 T effector (Teff) cell cytokine production and cytolytic activity, and KB oxidation (ketolysis) was required for Teff cell responses to bacterial infection and tumor challenge.
View Article and Find Full Text PDFArticle Synopsis
- Infusing 13C-labeled metabolites like glucose and glutamine in infected mice reveals how CD8+ T effector (Teff) cells utilize these substances for energy during immune responses.
- Early Teff cells primarily use glucose for nucleotide synthesis and glutamine for energy production in the TCA cycle, while depending on Got1 for aspartate synthesis necessary for their growth.
- Over the course of an infection, Teff cells shift their energy source from glutamine to acetate, highlighting the changing metabolic needs of these immune cells.