Abnormal natural killer cell function in systemic sclerosis: altered cytokine production and defective killing activity.
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.
Horikawa
Mayuka
M
Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
Hasegawa
Minoru
M
Komura
Kazuhiro
K
Hayakawa
Ikuko
I
Yanaba
Koichi
K
Matsushita
Takashi
T
Takehara
Kazuhiko
K
Sato
Shinichi
S
D000328:Adult; D000368:Aged; D016207:Cytokines / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D053804:Granzymes; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000276:immunology*; D012697:Serine Endopeptidases / Q000378:metabolism
D016207:Cytokines; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases