title: Autophagy, a novel pathway to regulate calcium mobilization in T lymphocytes.
abstract: The T lymphocyte response initiates with the recognition of MHC/peptides on antigen presenting cells by the T cell receptor (TCR). After the TCR engagement, the proximal signaling pathways are activated for downstream cellular events. Among these pathways, the calcium-signaling flux is activated through the depletion of endoplasmic reticulum (ER) calcium stores and plays pivotal roles in T cell proliferation, cell survival, and apoptosis. In studying the roles of macroautophagy (hereafter referred to as autophagy) in T cell function, we found that a pathway for intracellular degradation, autophagy, regulates calcium signaling by developmentally maintaining the homeostasis of the ER. Using mouse genetic models with specific deletion of autophagy-related genes in T lymphocytes, we found that the calcium influx is defective and the calcium efflux is increased in autophagy-deficient T cells. The abnormal calcium flux is related to the expansion of the ER and higher calcium stores in the ER. Because of this, treatment with the ER sarco/ER Ca(2+)-ATPase pump inhibitor, thapsigargin, rescues the calcium influx defect in autophagy-deficient T cells. Therefore, autophagy regulates calcium mobilization in T lymphocytes through ER homeostasis.
authors.affiliation: Department of Immunology, Duke University Medical Center Durham, NC, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.forename: Ming-Xiao
authors.initials: MX
authors.lastname: He
authors.forename: Ian X
authors.initials: IX
authors.lastname: McLeod
authors.forename: You-Wen
authors.initials: YW
authors.lastname: He
keywords: ER homeostasis; ER-phagy; T lymphocytes; autophagy; calcium flux