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Studies of natural killer cells in health and disease: a systematic review

Objective To review the role of natural killer cells (NKCs) in health and disease. Data sources A systematic search of MEDLINE (PubMed, Medscape, and Science Direct, EMF-Portal) and Internet was conducted on all articles published from 1982 to 2019. Regarding study selection, English-language reports of NKCs in health and disease were examined. The initial search presented 145 articles, where 30 satisfied the inclusion criteria. Data extraction Articles not reporting on NKCs in health and disease in the title or abstract were not included. Five independent investigators extracted data on methods. Data synthesis Comparisons were made by structured review, with the results tabulated. Nine studies reported about NKC function, 10 studies about NKCs during various phases of human life, and 11 studies emphasized on NKCs in various disease conditions. Findings Approximately 10% of NKCs belong to the CD56bright subset and mostly involved in the production of cytokines. NKCs are considered to have the ability to respond to a variety of stimuli and to participate in immune responses under different pathological conditions. Human NKCs are present in fetal liver as early as gestational week 6 and in fetal spleen at gestational week 15. NKCs are an important regulator of spiral artery remodeling and maintenance of decidual integrity. In most cases, the role of NKCs is found to be either disease controlling or disease enhancing. In many instances of autoimmune disease, a reduction in the number of NKCs along with decreased cytotoxic function has been observed. Conclusion The NKCs play a major role in human health and disease. Although persistent abnormalities in NKC activity or number appear to be associated with a wide spectrum of human diseases, evidence for the causal association of abnormally low NK activity with pathogenesis is so far available only from a limited number of experimental models.