Format

Send to

Choose Destination
See comment in PubMed Commons below
PLoS One. 2012;7(5):e33518. doi: 10.1371/journal.pone.0033518. Epub 2012 May 10.

Prostaglandin I2 signaling drives Th17 differentiation and exacerbates experimental autoimmune encephalomyelitis.

Author information

1
Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America. weisong.zhou@vanderbilt.edu

Abstract

BACKGROUND:

Prostaglandin I(2) (PGI(2)), a lipid mediator currently used in treatment of human disease, is a critical regulator of adaptive immune responses. Although PGI(2) signaling suppressed Th1 and Th2 immune responses, the role of PGI(2) in Th17 differentiation is not known.

METHODOLOGY/PRINCIPAL FINDINGS:

In mouse CD4(+)CD62L(+) naïve T cell culture, the PGI(2) analogs iloprost and cicaprost increased IL-17A and IL-22 protein production and Th17 differentiation in vitro. This effect was augmented by IL-23 and was dependent on PGI(2) receptor IP signaling. In mouse bone marrow-derived CD11c(+) dendritic cells (BMDCs), PGI(2) analogs increased the ratio of IL-23/IL-12, which is correlated with increased ability of BMDCs to stimulate naïve T cells for IL-17A production. Moreover, IP knockout mice had delayed onset of a Th17-associated neurological disease, experimental autoimmune encephalomyelitis (EAE), and reduced infiltration of IL-17A-expressing mononuclear cells in the spinal cords compared to wild type mice. These results suggest that PGI(2) promotes in vivo Th17 responses.

CONCLUSION:

The preferential stimulation of Th17 differentiation by IP signaling may have important clinical implications as PGI(2) and its analogs are commonly used to treat human pulmonary hypertension.

PMID:
22590492
PMCID:
PMC3349674
DOI:
10.1371/journal.pone.0033518
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Support Center