Abnormal natural killer cell function in systemic sclerosis: altered cytokine production and defective killing activity
Open accessAbstract
Natural killer (NK) cells are innate immune effectors that produce various immunoregulatory cytokines. Recent studies have shown that NK cells are involved in the initiation of autoimmunity. In this study, we determined abnormalities of NK cells in systemic sclerosis (SSc), an autoimmune connective tissue disease, by assessing the frequency and absolute number, activation marker expression, cytokine production, and killing activity. The frequency and absolute number of NK cells increased in diffuse cutaneous SSc (dcSSc), whereas they were normal in limited cutaneous SSc (lcSSc). NK cells from both dcSSc and lcSSc patients exhibited activated phenotypes characterized by up-regulated CD16 and CD69 expression and downregulated CD62L expression. Interferon (IFN)-gamma production by non-stimulated NK cells from both dcSSc and lcSSc patients was increased compared to the normal control, whereas on stimulation, a reduced amount of IFN-gamma was produced. Interleukin (IL)-5 and IL-10 production by non-stimulated NK cells and IL-6 production by stimulated NK cells were augmented in dcSSc patients, but not in lcSSc patients. Despite the augmented cytokine production by non-stimulated NK cells, natural cytotoxicity activity and granzyme B secretion was reduced in NK cells from dcSSc and lcSSc patients. These results suggested that altered NK cell function contributes to immunological abnormalities in SSc.
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NK cells produce IFNγ, a strong inhibitor of myofibroblast formation and function.
“Furthermore, NK cells produce IFNγ a strong inhibitor of myofibroblasts formation and function (171).”
From Unraveling SSc Pathophysiology; The Myofibroblast (2018) · cites this paper as [171]
In SSc, both the killing ability and stimulation-dependent IFNγ production of NK cells have been reported to be reduced.
“However, in SSc, both the killing ability and stimulation-dependent IFNγ production of NK cells has been reported to be reduced (171).”
From Unraveling SSc Pathophysiology; The Myofibroblast (2018) · cites this paper as [171]
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Unraveling SSc Pathophysiology; The Myofibroblast
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- Authors
- Horikawa, M., Hasegawa, M., Komura, K., Hayakawa, I., Yanaba, K., Matsushita, T., Takehara, K., & Sato, S.
- Affiliations
- Kanazawa University (JP)
- Corresponding author
- Sato, Shinichi
- ORCID
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 125
- Issue
- 4
- Pages
- 731-737
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W2010043145
- Cited by
- 72
- References
- 38
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 7 · 2021: 5 · 2020: 5 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 1 · 2015: 3 · 2014: 3 · 2013: 2 · 2012: 3
- FWCI
- 0.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Kanazawa University Repository for Academic Resources (DSpace) (Kanazawa University) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- natural killer cells, systemic sclerosis, diffuse cutaneous systemic sclerosis, limited cutaneous systemic sclerosis, NK cell activation, interferon-gamma, IL-5, IL-10, interleukin-6, granzyme B, natural cytotoxicity, autoimmunity, connective tissue diseases
- MeSH terms
- Adult, Aged, Cytotoxicity, Immunologic, Female, Flow Cytometry, Humans, Killer Cells, Natural, Male, Middle Aged, Scleroderma, Systemic, Serine Endopeptidases, Immunophenotyping, Cytokines, Lymphocyte Count, Granzymes
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