Date of Award

2025

Degree Name

Pharmaceutical Sciences

College

School of Pharmacy

Type of Degree

M.S.

Document Type

Thesis

First Advisor

Dr. Jeremy McAleer

Second Advisor

Dr. Timothy Long

Third Advisor

Dr. Hasan Koc

Abstract

T lymphocytes contribute to host defense and inflammation producing cytokines in response to antigenic stimuli. CD4 T cell activation induces dramatic changes to cellular metabolism for supporting their growth and differentiation into effector subsets. Distinct subsets have been named Th1, Th2, Th9, Th17, Th22, Tfh and Treg based on their characteristic effector cytokines and transcription factors expressed. Th9 cells are one of the most recent subsets identified. While the cytokines IL-4, TGF-β and IL-21 promote differentiation into Th9 cells, metabolic factors regulating this process remain poorly understood. We hypothesized that lipid metabolism could regulate Th9 cell differentiation which may have an impact on immune responses in inflammatory disorders. To assess the role of lipid metabolism in human Th9 cell differentiation, naïve CD4 T cells were purified from blood of healthy volunteers and cultured in the presence or absence of compounds targeting PPAR-γ, acetyl-CoA-carboxylase 1 (ACC1), and AMP-activated protein kinase (AMPK). Rosiglitazone, PPAR-γ agonist, resulting in a dose dependent suppression of IL-9 production that was not dependent on glycolytic pathways. On the other hand, ACC1 inhibition increased IL-9 expression, indicating that Th9 differentiation is suppressed by de novo fatty acid production. These results indicate possible metabolic targets for regulating Th9-mediated immune responses and show that lipid modulators have a significant impact on IL-9 production.

Subject(s)

T cells.

Cytokines.

Cell metabolism.

Transcription factors.

Lipids -- Metabolism.

Cell differentiation.

Immune response.

Inflammation -- Diseases.

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