title: In vivo activation of invariant natural killer T cells induces systemic and local alterations in T-cell subsets prior to preterm birth.
abstract: Preterm birth, the leading cause of neonatal morbidity and mortality worldwide, is frequently preceded by spontaneous preterm labour, a syndrome of multiple aetiologies. Pathological inflammation is causally linked to spontaneous preterm labour. Indeed, direct activation of invariant natural killer T (iNKT) cells via α-galactosylceramide induces preterm labour/birth largely by initiating systemic and local (i.e. decidua and myometrium) innate immune responses. Herein, we investigated whether iNKT-cell activation altered local and systemic T-cell subsets. Administration of α-galactosylceramide induced an expansion of activated CD1d-restricted iNKT cells in the decidua and a reduction in the number of: (1) total T cells (conventional CD4+and CD8+T cells) through the down-regulation of the CD3ɛ molecule in the peripheral circulation, spleen, uterine-draining lymph nodes (ULNs), decidua and/or myometrium; (2) CD4+regulatory T cells in the spleen, ULNs and decidua; (3) T helper type 17 (Th17) cells in the ULNs but an increase in the number of decidual Th17 cells; (4) CD8+regulatory T cells in the spleen and ULNs; and (5) CD4+and CD8+forkhead box protein 3 negative (Foxp3-) responder T cells in the spleen and ULNs. As treatment with rosiglitazone prevents iNKT-cell activation-induced preterm labour/birth, we also explored whether the administration of this peroxisome proliferator-activated receptor gamma (PPARγ) agonist would restore the number of T cells. Treating α-galactosylceramide-injected mice with rosiglitazone partially restored the number of T cells in the spleen but not in the decidua. In summary, iNKT-cell activation altered the systemic and local T-cell subsets prior to preterm labour/birth; however, treatment with rosiglitazone partially reversed such effects.
authors.affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, and Detroit, MI, USA.|Department of Obstetrics & Gynecology, Wayne State University, School of Medicine, Detroit, MI, USA.|Department of Immunology & Microbiology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: N
authors.identifier: 0000-0002-3406-5262
authors.initials: N
authors.lastname: Gomez-Lopez
authors.affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, and Detroit, MI, USA.|Department of Obstetrics & Gynecology, University of Michigan, Ann Arbor, MI, USA.|Department of Epidemiology & Biostatistics, Michigan State University, East Lansing, MI, USA.|Center for Molecular Medicine & Genetics, Wayne State University, Detroit, MI, USA.
authors.forename: R
authors.initials: R
authors.lastname: Romero
authors.affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, and Detroit, MI, USA.|Department of Obstetrics & Gynecology, Wayne State University, School of Medicine, Detroit, MI, USA.|Department of Molecular Biomedicine, CINVESTAV, Mexico City, Mexico.
authors.forename: M
authors.initials: M
authors.lastname: Arenas-Hernandez
authors.affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, and Detroit, MI, USA.|Department of Obstetrics & Gynecology, Wayne State University, School of Medicine, Detroit, MI, USA.
authors.forename: G
authors.initials: G
authors.lastname: Schwenkel
authors.affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, and Detroit, MI, USA.|Department of Obstetrics & Gynecology, Wayne State University, School of Medicine, Detroit, MI, USA.
authors.forename: D
authors.initials: D
authors.lastname: St Louis
authors.affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, and Detroit, MI, USA.|Department of Obstetrics & Gynecology, Wayne State University, School of Medicine, Detroit, MI, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Hassan
authors.affiliation: Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, MD, and Detroit, MI, USA.|Department of Obstetrics & Gynecology, Wayne State University, School of Medicine, Detroit, MI, USA.
authors.forename: T N
authors.initials: TN
authors.lastname: Mial
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005699:Galactosylceramides; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology*; D047495:PPAR gamma / Q000819:agonists*; D011247:Pregnancy; D047928:Premature Birth / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D000077154:Rosiglitazone; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D045162:Thiazolidinediones / Q000008:administration & dosage*
chemical_list: D016207:Cytokines; D005699:Galactosylceramides; D047495:PPAR gamma; D045162:Thiazolidinediones; C493154:alpha-galactosylceramide; D000077154:Rosiglitazone
keywords: PPARγ; cytokine; inflammation; parturition; pregnancy; prematurity; preterm labour; rosiglitazone