{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T06:05:41Z","timestamp":1780553141923,"version":"3.54.1"},"reference-count":114,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Natural killer (NK) cells show day\u2013night variation in both number and effector function. We compile findings from human cohorts, animal models, and cell studies on how circadian timing shapes NK biology. Evidence spans daily changes in counts and readouts such as degranulation and IFN-\u03b3; links to core clock modules (PER1\/2, NFIL3\/E4BP4, STRA13); and neuroendocrine inputs (sympathetic tone, glucocorticoids, melatonin). Acute sleep loss can transiently raise NK activity, whereas multi-day sleep deprivation or circadian misalignment lowers counts or function. Shift work studies and laboratory night-shift simulations show reductions in NK activity and phase-sensitive changes in transcriptional programs (e.g., AP-1\/STAT), with effects amplified by irregular schedules and accumulated fatigue. Across cancer, depression, vitiligo, and infection, alterations are heterogeneous, often presenting as peak shifts or amplitude flattening rather than loss of rhythmicity. Photoperiod, season, age, and sex can modify these patterns. Current data support a circadian influence on NK biology, but the direction and magnitude of reported effects vary across species, sampling schedules, circadian phase definitions, tissue compartments, and NK-cell readouts. This heterogeneity underscores the need for longitudinal, high-frequency sampling with complementary continuous monitoring to define phase, amplitude, and stability across physiological and clinical contexts.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1739723","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T05:35:26Z","timestamp":1780551326000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clocking immunity: circadian modulation of NK cells and emerging timing perspectives"],"prefix":"10.3389","volume":"17","author":[{"given":"Kun","family":"Liu","sequence":"first","affiliation":[{"name":"Third Affiliated Hospital of Naval Medical University (Second Military Medical University), National Center for Liver Cancer","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanying","family":"Lv","sequence":"additional","affiliation":[{"name":"Third Affiliated Hospital of Naval Medical University (Second Military Medical University), National Center for Liver Cancer","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Wen","sequence":"additional","affiliation":[{"name":"Third Affiliated Hospital of Naval Medical University (Second Military Medical University), National Center for Liver Cancer","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0008-4","article-title":"Clocking in to immunity","volume":"18","author":"Scheiermann","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2025.104632","article-title":"Rhythm is essential: Unraveling the relation between the circadian clock and cancer","volume":"208","author":"Ogunlusi","year":"2025","journal-title":"Crit Rev Oncol Hematol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/biom11040487","article-title":"Biological rhythm and chronotype: New perspectives in health","volume":"11","author":"Montaruli","year":"2021","journal-title":"Biomolecules"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abm2465","article-title":"The circadian immune system","volume":"7","author":"Wang","year":"2022","journal-title":"Sci Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13747","article-title":"Circadian rhythm regulation in the immune system","volume":"171","author":"Ding","year":"2024","journal-title":"Immunology"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/pim.12903","article-title":"The involvement of host circadian clocks in the regulation of the immune response to parasitic infections in mammals","volume":"44","author":"Carvalho Cabral","year":"2022","journal-title":"Parasite Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2021.114701","article-title":"REV-ERB\u03b1 agonist SR9009 suppresses IL-1\u03b2 production in macrophages through BMAL1-dependent inhibition of inflammasome","volume":"192","author":"Hong","year":"2021","journal-title":"Biochem Pharmacol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16088","article-title":"Chronic shift-lag promotes NK cell ageing and impairs immunosurveillance in mice by decreasing the expression of CD122","volume":"24","author":"Zeng","year":"2020","journal-title":"J Cell Mol Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15020408","article-title":"Role of clock genes and circadian rhythm in renal cell carcinoma: Recent evidence and therapeutic consequences","volume":"15","author":"Santoni","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B10","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1186\/s40164-024-00561-z","article-title":"Natural killer cell-based cancer immunotherapy: From basics to clinical trials","volume":"13","author":"Shi","year":"2024","journal-title":"Exp Hematol Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-007-9501-z","article-title":"Are circadian rhythms the code of hypothalamic-immune communication? 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