Absence of the Adaptor Protein PEA-15 Is Associated with Altered Pattern of Th Cytokines Production by Activated CD4+ T Lymphocytes In Vitro, and Defective Red Blood Cell Alloimmune Response In Vivo

PloS One
Stéphane KerbratSabine Le Gouvello

Abstract

TCR-dependent and costimulation signaling, cell division, and cytokine environment are major factors driving cytokines expression induced by CD4(+) T cell activation. PEA-15 15 (Protein Enriched in Astrocyte / 15 kDa) is an adaptor protein that regulates death receptor-induced apoptosis and proliferation signaling by binding to FADD and relocating ERK1/2 to the cytosol, respectively. By using PEA-15-deficient mice, we examined the role of PEA-15 in TCR-dependent cytokine production in CD4(+) T cells. TCR-stimulated PEA-15-deficient CD4(+) T cells exhibited defective progression through the cell cycle associated with impaired expression of cyclin E and phosphoRb, two ERK1/2-dependent proteins of the cell cycle. Accordingly, expression of the division cycle-dependent cytokines IL-2 and IFNγ, a Th1 cytokine, was reduced in stimulated PEA-15-deficient CD4(+) T cells. This was associated with abnormal subcellular compartmentalization of activated ERK1/2 in PEA-15-deficient T cells. Furthermore, in vitro TCR-dependent differentiation of naive CD4(+) CD62L(+) PEA-15-deficient T cells was associated with a lower production of the Th2 cytokine, IL-4, whereas expression of the Th17-associated molecule IL4I1 was enhanced. Finally, a defec...Continue Reading

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Citations

Feb 10, 2016·Trends in Biochemical Sciences·Sara CogliatiLuca Scorrano
Oct 18, 2016·Current Opinion in Hematology·Jeanne E HendricksonChristopher A Tormey
Apr 18, 2020·Scientific Reports·Indoumady BaskaraSabine Le Gouvello
Nov 7, 2019·International Journal of Radiation Oncology, Biology, Physics·Hoang Quy NguyenSabine Le Gouvello

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Methods Mentioned

BETA
flow cytometry
PCR
ELISA
PMA

Software Mentioned

FlowJo
CXP
Prism
Image Quant
GraphPad

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