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- Title
In vivo activation of invariant natural killer T cells induces systemic and local alterations in T-cell subsets prior to preterm birth.
- Authors
Gomez‐Lopez, N.; Romero, R.; Arenas‐Hernandez, M.; Schwenkel, G.; St Louis, D.; Hassan, S. S.; Mial, T. N.
- 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.
- Subjects
KILLER cells; PREMATURE labor; ROSIGLITAZONE; GALACTOSYLCERAMIDES; IN vivo studies; THERAPEUTICS
- Publication
Clinical & Experimental Immunology, 2017, Vol 189, Issue 2, p211
- ISSN
0009-9104
- Publication type
Article
- DOI
10.1111/cei.12968