Regulation of the allergic airway Th2 response by redox metabolism

Project Details

Description

T helper-2 (Th2) cells are crucial in allergic inflammation. The complete transcriptional profile of Th2 cells has recently been elucidated by single-cell RNA sequencing (scRNA-seq) of T helper cells in the house dust mite model of allergic airway disease. The scRNA-Seq results pinpointed to a gene expression signature in Th2 cells that was highly enriched for Il1rl1 (ST2), Gata3, Il13, Il5, Ltb4r1, Plac8, and Pparg, all indicative of a pathologic Th2 cell phenotype. Other highly expressed genes not previously associated with Th2-cell immunity were found to be expressed in allergic airways, including Gclc, the gene for the catalytic subunit of glutamate cysteine ligase (GCL). GCL is catalyzing the rate-limiting step in glutathione (GSH) synthesis. Activated T cells control their intracellular reactive oxygen species particularly by GSH. To date, the role of GSH and of redox metabolism has not been addressed in a mechanistic approach during Th2 responses in IgE-mediated allergy. We will analyze conditional mutant mice lacking Gclc specifically in Th/Th2 cells using allergic asthma disease models developed by us. By targeting Gclc in T cells, Prof. Brenner’s group has demonstrated that antioxidation by GSH supports an environment essential for activation-induced metabolic reprogramming in T cells during antiviral and autoimmune responses. As key metabolic pathways (glucose and lipid metabolism) have also been demonstrated in Th2 cells during allergic inflammation, we expect a change in the phenotypic disease outcome during allergen re-exposure in an allergic asthma model in mice with Gclc deficiency in Th/Th2 cells.
AcronymNextimmune-2 (Andrea Riviello)
StatusActive
Effective start/end date15/01/2414/01/28

Funding

  • FNR - Fonds National de la Recherche: €186,000.00

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