Regulation of immune responses by prostaglandin E2

P Kalinski - The Journal of Immunology, 2012 - journals.aai.org
The Journal of Immunology, 2012journals.aai.org
PGE 2, an essential homeostatic factor, is also a key mediator of immunopathology in
chronic infections and cancer. The impact of PGE 2 reflects the balance between its
cyclooxygenase 2-regulated synthesis and 15-hydroxyprostaglandin dehydrogenase-driven
degradation and the pattern of expression of PGE 2 receptors. PGE 2 enhances its own
production but suppresses acute inflammatory mediators, resulting in its predominance at
late/chronic stages of immunity. PGE 2 supports activation of dendritic cells but suppresses …
Abstract
PGE 2, an essential homeostatic factor, is also a key mediator of immunopathology in chronic infections and cancer. The impact of PGE 2 reflects the balance between its cyclooxygenase 2-regulated synthesis and 15-hydroxyprostaglandin dehydrogenase-driven degradation and the pattern of expression of PGE 2 receptors. PGE 2 enhances its own production but suppresses acute inflammatory mediators, resulting in its predominance at late/chronic stages of immunity. PGE 2 supports activation of dendritic cells but suppresses their ability to attract naive, memory, and effector T cells. PGE 2 selectively suppresses effector functions of macrophages and neutrophils and the Th1-, CTL-, and NK cell-mediated type 1 immunity, but it promotes Th2, Th17, and regulatory T cell responses. PGE 2 modulates chemokine production, inhibiting the attraction of proinflammatory cells while enhancing local accumulation of regulatory T cells cells and myeloid-derived suppressor cells. Targeting the production, degradation, and responsiveness to PGE 2 provides tools to modulate the patterns of immunity in a wide range of diseases, from autoimmunity to cancer.
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