Metabolic Control of T follicular helper cell polarization

Anthony Mendoza

Document Type

Article

Publication Date

Summer 2022

Keywords

JMG

JAX Location

In: Student Reports, Summer 2022, The Jackson Laboratory

Abstract

T cells are critical to the adaptive immune system protecting the body against pathogens and tumors. Activated T cells change their metabolic state to meet their new effector functions. T follicular helper cells (Tfh) are a subtype of CD4+ T cells helping germinal center B cells survive and develop into antibody-producing plasma cells during an immune response. This research studied downstream metabolites of the tryptophan pathway to determine metabolic candidates for improving Tfh-cell yield efficiency for in vitro culturing methods. Metabolic pathways affecting Tfh-cell induction were examined to determine the role of tryptophan and metabolism in the immune system and Tfh-cell differentiation. CD4+ T cells expressed increased Tfh markers under glycolysis inhibition, but the opposite effect was seen in fatty acid oxidation (FAO), glutaminolysis, and oxidative phosphorylation (OXPHOS) inhibition. Polarized Tfh-cell fold change and Tfh markers also increased towards the cinnabarinic acid branch of the tryptophan pathway. This indicates the importance of FAO, glutaminolysis, and OXPHOS dependency for Tfh-cell markers and the cinnabarinic acid branch’s role in Tfh-cell marker and gene expression. This also demonstrates that the tryptophan pathway is a promising route for increased Tfh-cell yield efficiency. Future research will have to validate whether these cells with Tfh phenotypes are functionally comparable to in vivo Tfh cells.

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