A PD-1-ST2 axis controls Th2 effector function in tissue via a metabolic checkpoint
Heieis, G. A.; Everts, B.; Roberts, C. W.; Maizels, R. M.; Perona-Wright, G.
Show abstract
Type 2 immune responses characterise both helminth infections and atopic disease such as allergy or asthma, but a better understanding of the mechanisms that regulate these responses is key to improving therapeutic and vaccination strategies. Immuno-metabolic studies over the last two decades have suggested T cell activation broadly requires rapid increases in glycolysis and oxidative phosphorylation. In contrast, we show that CD4+ T helper 2 (Th2) cells activated in vivo, using models of helminth infection, do not acquire a glycolytic metabolism. Instead, we show that Th2 cells solely increase their oxidative metabolism, associated with increased fatty acid uptake. Rather than contributing directly to effector function, our data reveal that Th2 cells switch to fatty acid oxidation downstream of PD-1 signalling to promote expression of the IL-33 receptor (ST2). These data provide insight into the spatial regulation of T cell metabolism, and suggest that PD-1 blockade therapies may be effective in Th2 disorders.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Microbiota promote enhanced CD39 expression in γδ intraepithelial lymphocytes through the activation of TCR and IL-15 signaling 97%
- Trained ILC2 prevent IL-17-associated lung injury during helminth infection through a serotonin-dependent mechanism 96%
- Tissue-based IL-10 signalling in helminth infection limits IFNγ expression and promotes the intestinal Th2 response 96%
Similar papers in this journal
- Early and Delayed STAT1-Dependent Responses Drive Local Trained Immunity of Macrophages in the Spleen 96%
- Longitudinal analysis of invariant natural killer T cell activation reveals a cMAF-associated transcriptional state of NKT10 cells 96%
- Oxygen levels at the time of activation determine T cell persistence and immunotherapeutic efficacy 96%
Similar papers in this journal
- MAIT cells protect against sterile lung injury 96%
- Stearoyl-CoA desaturase mediated monounsaturated fatty acid availability supports humoral immunity 96%
- The pseudokinase Trib1 regulates the transition of exhausted T cells to a KLR+ CD8+ effector state and its deletion improves checkpoint blockade 96%
Similar papers in this journal
- Metformin enhances anti-mycobacterial responses by educating immunometabolic circuits of CD8+ T cells 98%
- Transcriptome and Chromatin Landscape of iNKT cells are Shaped by Subset Differentiation and Antigen Exposure 96%
- A Two-Step Activation Mechanism Enables Mast Cells to Differentiate their Response between Extracellular and Invasive Enterobacterial Infection 96%
Similar papers in this journal
- TLR2 Supports γδ T cell IL-17A Response to ocular surface commensals by Metabolic Reprogramming 96%
- Amino acid availability acts as a metabolic rheostat to determine the magnitude of ILC2 responses 96%
- HDAC1 controls the generation and maintenance of effector-like CD8+ T cells during chronic viral infection 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.