Metabolic Control of T follicular helper cell polarization

Authors

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.

Please contact the Joan Staats Library for information regarding this document.

COinS