Master of Science
Physiology and Pharmacology
Dr. Wei-Yang Lu
In response to antigen presentation, helper T lymphocytes (TH cells) initiate store-operated Ca2+ entry (SOCE) and differentiate into effector subtypes such as TH1 and TH2 cells. These cells play essential roles in adaptive immunity and the pathogenesis of various autoimmune and allergic diseases. The differentiation and activity of TH cells are also critically regulated by paracrine and autocrine soluble factors in the cell microenvironment. Previous studies have reported that TH cells produce gamma-aminobutyric acid (GABA) via glutamic acid decarboxylase (GAD) and express A-type GABA receptors (GABAARs), forming an autocrine GABA signaling system. In addition, GABA executes anti-inflammatory actions in TH1-autoimmune diseases. This project sought to examine whether autocrine GABA signaling distinctively regulates the function of different TH effector cells using two unique lines of human TH cells: Jurkat and CCRF-CEM. Our results showed that Jurkat and CCRF-CEM cells exhibited features of TH1 and TH2 phenotypes, respectively, and express different levels of GABAAR subunits. Selective blockade of GABAARs 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 TH subtypes.
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.
Available for download on Thursday, August 01, 2019