title: Human monocytes have increased IFN-γ-mediated IL-15 production with age alongside altered IFN-γ receptor signaling.
abstract: IL-15 is involved in regulating host defense and inflammation. Monocytes produce the biologically active cell surface IL-15 in response to IFN-γ. Although aging can alter the immune system, little is known about whether and how aging affects IFN-γ-mediated IL-15 production in human monocytes. We showed that monocytes of healthy older adults (age ≥ 65) had increased cell surface IL-15 expression in response to IFN-γ compared to those of healthy young adults (age ≤ 40). This finding stems in part from increased IFN-γ receptor (R)1/2 expression on monocytes in older adults, leading to enhanced STAT1 activation and interferon regulatory factor 1 synthesis with increased IL15 gene expression. Our study suggests that with aging the IFN-γ-mediated IL-15 production pathway in human monocytes is uncompromised, but rather augmented, and could be considered as a therapeutic target point to modulate host defense and inflammation in older adults.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Naeun
authors.initials: N
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Min Sun
authors.initials: MS
authors.lastname: Shin
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Pediatrics, Jeju National University School of Medicine, Jeju 690-756, Republic of Korea.
authors.forename: Ki Soo
authors.initials: KS
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Seung-Ah
authors.initials: SA
authors.lastname: Yoo
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Subhasis
authors.initials: S
authors.lastname: Mohanty
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Montgomery
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Shaw
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: Insoo.kang@yale.edu.
authors.forename: Insoo
authors.initials: I
authors.lastname: Kang
mesh_terms: D000328:Adult; D000367:Age Factors; D000375:Aging / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D050856:Interferon Regulatory Factor-1 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000378:metabolism*; D019409:Interleukin-15 / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D017471:Receptors, Interferon / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D053647:Receptors, Interleukin-15 / Q000276:immunology / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D000096743:Interferon gamma Receptor
chemical_list: D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma; D019409:Interleukin-15; D017471:Receptors, Interferon; D053647:Receptors, Interleukin-15; D050794:STAT1 Transcription Factor; D000096743:Interferon gamma Receptor; C508024:IL15RA protein, human; C494257:IRF1 protein, human; C494079:STAT1 protein, human
keywords: Human; IFN-γ; IL-15; Monocytes and aging