title: Partial sleep restriction activates immune response-related gene expression pathways: experimental and epidemiological studies in humans.
abstract: Epidemiological studies have shown that short or insufficient sleep is associated with increased risk for metabolic diseases and mortality. To elucidate mechanisms behind this connection, we aimed to identify genes and pathways affected by experimentally induced, partial sleep restriction and to verify their connection to insufficient sleep at population level. The experimental design simulated sleep restriction during a working week: sleep of healthy men (N = 9) was restricted to 4 h/night for five nights. The control subjects (N = 4) spent 8 h/night in bed. Leukocyte RNA expression was analyzed at baseline, after sleep restriction, and after recovery using whole genome microarrays complemented with pathway and transcription factor analysis. Expression levels of the ten most up-regulated and ten most down-regulated transcripts were correlated with subjective assessment of insufficient sleep in a population cohort (N = 472). Experimental sleep restriction altered the expression of 117 genes. Eight of the 25 most up-regulated transcripts were related to immune function. Accordingly, fifteen of the 25 most up-regulated Gene Ontology pathways were also related to immune function, including those for B cell activation, interleukin 8 production, and NF-κB signaling (P<0.005). Of the ten most up-regulated genes, expression of STX16 correlated negatively with self-reported insufficient sleep in a population sample, while three other genes showed tendency for positive correlation. Of the ten most down-regulated genes, TBX21 and LGR6 correlated negatively and TGFBR3 positively with insufficient sleep. Partial sleep restriction affects the regulation of signaling pathways related to the immune system. Some of these changes appear to be long-lasting and may at least partly explain how prolonged sleep restriction can contribute to inflammation-associated pathological states, such as cardiometabolic diseases.
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
authors.forename: Vilma
authors.initials: V
authors.lastname: Aho
authors.forename: Hanna M
authors.initials: HM
authors.lastname: Ollila
authors.forename: Ville
authors.initials: V
authors.lastname: Rantanen
authors.forename: Erkki
authors.initials: E
authors.lastname: Kronholm
authors.forename: Ida
authors.initials: I
authors.lastname: Surakka
authors.forename: Wessel M A
authors.initials: WM
authors.lastname: van Leeuwen
authors.forename: Maili
authors.initials: M
authors.lastname: Lehto
authors.forename: Sampsa
authors.initials: S
authors.lastname: Matikainen
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
authors.forename: Mikko
authors.initials: M
authors.lastname: Härmä
authors.forename: Mikael
authors.initials: M
authors.lastname: Sallinen
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.forename: Harri
authors.initials: H
authors.lastname: Alenius
authors.forename: Tiina
authors.initials: T
authors.lastname: Paunio
authors.forename: Tarja
authors.initials: T
authors.lastname: Porkka-Heiskanen
mesh_terms: D000328:Adult; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D046228:Microarray Analysis; D016328:NF-kappa B / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D012313:RNA / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D050794:STAT1 Transcription Factor; D012892:Sleep Deprivation / Q000276:immunology*; D051438:Syntaxin 16 / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: C417544:LGR6 protein, human; D016328:NF-kappa B; D011509:Proteoglycans; D043562:Receptors, G-Protein-Coupled; D018125:Receptors, Transforming Growth Factor beta; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C496118:STX16 protein, human; D051438:Syntaxin 16; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C071736:betaglycan; D012313:RNA