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

Zhou W, Dowell DR, Huckabee MM, Newcomb DC, Boswell MG, Goleniewska K, Lotz MT, Toki S, Yin H, Yao S, Natarajan C, Wu P, Sriram S, Breyer RM, Fitzgerald GA, Peebles RS
PLoS One. 2012 7 (5): e33518

PMID: 22590492 · PMCID: PMC3349674 · DOI:10.1371/journal.pone.0033518

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.

MeSH Terms (19)

Animals Antineoplastic Agents Cell Differentiation Cells, Cultured Encephalomyelitis, Autoimmune, Experimental Epoprostenol Female Humans Iloprost Interleukin-12 Interleukin-17 Interleukin-23 Mice Mice, Inbred BALB C Mice, Knockout Platelet Aggregation Inhibitors Receptors, Epoprostenol Spinal Cord Th17 Cells

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