title: Prostaglandin I2 signaling drives Th17 differentiation and exacerbates experimental autoimmune encephalomyelitis.
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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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
authors.forename: Weisong
authors.initials: W
authors.lastname: Zhou
authors.forename: Dustin R
authors.initials: DR
authors.lastname: Dowell
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Huckabee
authors.forename: Dawn C
authors.initials: DC
authors.lastname: Newcomb
authors.forename: Madison G
authors.initials: MG
authors.lastname: Boswell
authors.forename: Kasia
authors.initials: K
authors.lastname: Goleniewska
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Lotz
authors.forename: Shinji
authors.initials: S
authors.lastname: Toki
authors.forename: Huiyong
authors.initials: H
authors.lastname: Yin
authors.forename: Songyi
authors.initials: S
authors.lastname: Yao
authors.forename: Chandramohan
authors.initials: C
authors.lastname: Natarajan
authors.forename: Pingsheng
authors.initials: P
authors.lastname: Wu
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Sriram
authors.forename: Richard M
authors.initials: RM
authors.lastname: Breyer
authors.forename: Garret A
authors.initials: GA
authors.lastname: Fitzgerald
authors.forename: R Stokes
authors.initials: RS
authors.lastname: Peebles
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D006801:Humans; D016285:Iloprost / Q000276:immunology / Q000494:pharmacology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D053759:Interleukin-23 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010975:Platelet Aggregation Inhibitors / Q000276:immunology / Q000494:pharmacology*; D044006:Receptors, Epoprostenol / Q000235:genetics / Q000276:immunology*; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; C098680:Il17a protein, mouse; D020381:Interleukin-17; D053759:Interleukin-23; D010975:Platelet Aggregation Inhibitors; D044006:Receptors, Epoprostenol; D018664:Interleukin-12; D011464:Epoprostenol; D016285:Iloprost; C043867:cicaprost