Modulatory effects of the tumor suppressor p53 in T cell activation and function (original) (raw)

The Journal of Immunology, 2012

Abstract

Compelling evidence demonstrates that the tumor suppressor p53 plays important roles in regulating physiological functions, such as stem cell state, development, tissue homeostasis, inflammation, metabolism, and aging. Early immunological studies showed that p53 is rapidly activated upon TCR stimulation. Nevertheless, the mechanism that underlies the TCR-mediated p53 activation is unclear. Recently, we reported that p53 negatively regulates Th17 differentiation. Here, we further examined the function of p53 during non-polarizing T cell activation. Upon TCR stimulation (α-CD3+ α-CD28), especially under suboptimal conditions (low level of α-CD3), p53null T cells proliferated more aggressively with a higher effector function than their WT counterparts. To investigate the molecular mechanism by which p53 modulates T helper differentiation, we examined their gene expression via microarray. Among the 45,000 probe sets hybridized, 4025 genes within the Gene Ontology (GO) pathways of immune responses (innate immunity, IL-1β, IL-6, and IL-17 pathways), DNA damage responses, Cell cycle regulation, apoptosis, and survival showed significant differences (p

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