{"doi":"10.1016/j.celrep.2021.109595","title":"Chronic stress primes innate immune responses in mice and humans","abstract":"Psychological stress (PS) is associated with systemic inflammation and accelerates inflammatory disease progression (e.g., atherosclerosis). The mechanisms underlying stress-mediated inflammation and future health risk are poorly understood. Monocytes are key in sustaining systemic inflammation, and recent studies demonstrate that they maintain the memory of inflammatory insults, leading to a heightened inflammatory response upon rechallenge. We show that PS induces remodeling of the chromatin landscape and transcriptomic reprogramming of monocytes, skewing them to a primed hyperinflammatory phenotype. Monocytes from stressed mice and humans exhibit a characteristic inflammatory transcriptomic signature and are hyperresponsive upon stimulation with Toll-like receptor ligands. RNA and ATAC sequencing reveal that monocytes from stressed mice and humans exhibit activation of metabolic pathways (mTOR and PI3K) and reduced chromatin accessibility at mitochondrial respiration-associated loci. Collectively, our findings suggest that PS primes the reprogramming of myeloid cells to a hyperresponsive inflammatory state, which may explain how PS confers inflammatory disease risk.","journal":"Cell Reports","year":2021,"id":147465,"datarank":3.0778690208712893,"base_score":5.0689042022202315,"endowment":5.0689042022202315,"self_citation_contribution":0.7603356303330349,"citation_network_contribution":2.3175333905382542,"self_endowment_contribution":0.7603356303330349,"citer_contribution":2.3175333905382542,"corpus_percentile":null,"corpus_rank":null,"citation_count":158,"citer_count":100,"citers_with_citation_signal":100,"citers_with_endowment":100,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03022552"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":238960,"name":"Emma M. 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