Distinct Roles of GABA(A)R Signaling in the Regulation of Two Human T lymphocyte Lines

Author

Ying Lin, The University of Western OntarioFollow

Degree

Master of Science

Program

Physiology and Pharmacology

Supervisor

Dr. Wei-Yang Lu

Abstract

In response to antigen presentation, helper T lymphocytes (T_H cells) initiate store-operated Ca²⁺ entry (SOCE) and differentiate into effector subtypes such as T_H1 and T_H2 cells. These cells play essential roles in adaptive immunity and the pathogenesis of various autoimmune and allergic diseases. The differentiation and activity of T_H cells are also critically regulated by paracrine and autocrine soluble factors in the cell microenvironment. Previous studies have reported that T_H cells produce gamma-aminobutyric acid (GABA) via glutamic acid decarboxylase (GAD) and express A-type GABA receptors (GABA_ARs), forming an autocrine GABA signaling system. In addition, GABA executes anti-inflammatory actions in T_H1-autoimmune diseases. This project sought to examine whether autocrine GABA signaling distinctively regulates the function of different T_H effector cells using two unique lines of human T_H cells: Jurkat and CCRF-CEM. Our results showed that Jurkat and CCRF-CEM cells exhibited features of T_H1 and T_H2 phenotypes, respectively, and express different levels of GABA_AR subunits. Selective blockade of GABA_ARs differentially affected cell metabolic activity, CRTh2 expression, NFAT expression, and store-operated Ca²⁺ entry (SOCE) in the two cell lines. In conclusion, our results suggest that by modulating SOCE, autocrine GABA signaling uniquely regulates the activity of different T_H subtypes.

Recommended Citation

Lin, Ying, "Distinct Roles of GABA(A)R Signaling in the Regulation of Two Human T lymphocyte Lines" (2017). Electronic Thesis and Dissertation Repository. 4742.
https://ir.lib.uwo.ca/etd/4742