The lack of either IRF9, or STAT2, has surprisingly little effect on human natural killer cell development and function.

Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 0374672 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2567 (Electronic) Linking ISSN: 00192805 NLM ISO Abbreviation: Immunology Subsets: MEDLINE

Original Publication: Oxford : Blackwell Scientific Publications

Killer Cells, Natural*/immunology ; Killer Cells, Natural*/metabolism ; STAT2 Transcription Factor*/metabolism ; STAT2 Transcription Factor*/genetics ; Interferon-Stimulated Gene Factor 3, gamma Subunit*/metabolism ; Interferon-Stimulated Gene Factor 3, gamma Subunit*/genetics ; Interferon Type I*/metabolism ; Signal Transduction*; Humans ; Mutation ; Cell Differentiation ; STAT1 Transcription Factor/metabolism ; STAT1 Transcription Factor/genetics ; Cells, Cultured

Analysis of genetically defined immunodeficient patients allows study of the effect of the absence of specific proteins on human immune function in real-world conditions. Here we have addressed the importance of type I interferon signalling for human NK cell development by studying the phenotype and function of circulating NK cells isolated from patients suffering primary immunodeficiency disease due to mutation of either the human interferon regulatory factor 9 (IRF9) or the signal transducer and activator of transcription 2 (STAT2) genes. IRF9, together with phosphorylated STAT1 and STAT2, form a heterotrimer called interferon stimulated gene factor 3 (ISGF3) which promotes the expression of hundreds of IFN-stimulated genes that mediate antiviral function triggered by exposure to type I interferons. IRF9- and STAT2-deficient patients are unable to respond efficiently to stimulation by type I interferons and so our experiments provide insights into the importance of type I interferon signalling and the consequences of its impairment on human NK cell biology. Surprisingly, the NK cells of these patients display essentially normal phenotype and function.
(© 2024 The Authors. Immunology published by John Wiley & Sons Ltd.)

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PI16/01605 Carlos III Health Institute; PID2020-115506RB-I00 Secretaría de Estado de Investigación, Desarrollo e Innovación; SAF2017-83265-R Secretaría de Estado de Investigación, Desarrollo e Innovación; Spanish Association Against Cancer

Keywords: NK cell; cytokines; immune deficiencies

0 (STAT2 Transcription Factor)
0 (Interferon-Stimulated Gene Factor 3, gamma Subunit)
0 (IRF9 protein, human)
0 (Interferon Type I)
0 (STAT2 protein, human)
0 (STAT1 Transcription Factor)

Date Created: 20240322 Date Completed: 20240606 Latest Revision: 20240614

20240614

10.1111/imm.13779

38514903