T cell proliferation and adaptive immune responses are critically regulated by protein phosphatase 4. Issue 8 (17th April 2016)

• Record Type: Journal Article
• Authors: Liao, Fang-Hsuean; Hsiao, Wan-Yi; Lin, Yu-Chun; Chan, Yi-Chiao; Huang, Ching-Yu
• Is Part Of: Cell cycle. Volume 15:Issue 8(2016)
• Page Start: 1073
• Page End: 1083
• Publication Date: 2016-04-17
• Subjects: Conditional knockout -- G1-S arrest -- metabolism -- phosphatase -- T cell proliferation; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2016.1156267
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: The clonal expansion of activated T cells is pivotal for the induction of protective immunity. Protein phosphatase 4 (PP4) is a ubiquitously expressed serine/threonine phosphatase with reported functions in thymocyte development and DNA damage responses. However, the role of PP4 in T cell immunity has not been thoroughly investigated. In this report, our data showed that T cell-specific ablation of PP4 resulted in defective adaptive immunity, impaired T cell homeostatic expansion, and inefficient T cell proliferation. This hypo-proliferation was associated with a partial G1-S cell cycle arrest, enhanced transcriptions of CDK inhibitors and elevated activation of AMPK. In addition, resveratrol, a known AMPK activator, induced similar G1-S arrests, while lentivirally-transduced WT or constitutively-active AMPKα1 retarded the proliferation of WT T cells. Further investigations showed that PP4 co-immunoprecipitated with AMPKα1, and the over-expression of PP4 inhibited AMPK phosphorylation, thereby implicating PP4 for the negative regulation of AMPK. In summary, our results indicate that PP4 is an essential modulator for T cell proliferation and immune responses; they further suggest a potential link between PP4 functions, AMPK activation and G1-S arrest in activated T cells.