Background Natural killer cells (NK cells) are granular lymphocytes that belong to innate immunity, its major function is the lysis of virus-infected or tumoral cells. These functions are regulated by activating (NKG2D, NKp46, NKP30, NKG2C, CD161) and inhibitory receptors like KIRs and NKG2A. The role of NK cells in autoimmunity is poorly understood; it is well known that in systemic lupus erythematosus (SLE) patients there are decreased levels of NK cells. NK cells can modulate the adaptive immunity through its interaction with dendritic cells (DCs); the activation or killing of DC by NK cells depends of the ratio NK:DC. However, the interactions NK:DC in SLE have not been well studied. A new subset of NK cells with DCs characteristics has been reported in a model of lupus mice; however, the possible increment of NK cells with DC like phenotype in SLE has not been reported.
Objectives To analyze the phenotype of circulating NK cells as well as its function in SLE patients.
Methods Sixty SLE patients and fifty-five controls were included in this study. Diagnosis was made according to ACR criteria. Activity of disease was measured by SLEDAI index. The expression of NKG2A, ILT2, NKG2D, NKG2C, NKp30, NKp46, CD161, CD134, CD80, CD86, HLA-DR, CD11c+ was evaluated in NK cells (CD3-CD56+) from peripheral mononuclear cells. NK cell function was assessed by the percentage of monocyte-derived DC lysis by NK cells.
Results Diminished levels of circulating NK cells were found in SLE patients (p=0.0439) compared to healthy subjects. NK cells from SLE showed higher levels of the inhibitory receptor ILT2+(p=0.0024), and the costimulatory molecules CD86+ (p=0.0136) and CD134+(p=0.0238); in addition, SLE patients displayed a higher expression of MHC-class II molecule, HLA-DR+ (p<0.0001). Interestingly, higher levels of atypical NK cells CD11c+HLA-DR+ (p=0.0075) were found in SLE patients compared with healthy subjects. Furthermore, we found that SLE patients showed a significate increased level of monocyte derived-DC lysis by NK cells.
Conclusions In this study, we show for the first time that NK cells in SLE have an altered phenotype, expressing receptors, which are characteristic of dendritic cells (CD134, CD86 and HLA-DR). The expression of these receptors may provide NK cells with the ability to activate T cells, which together with their higher capacity to lyse immature or tolerogenic DCs could contribute to SLE pathogenesis. It is known that NK cells could have a dual role in autoimmune diseases, here we propose that the lysis of DC mediated by NK cells could be important to modulate the disease activity in SLE patients. Even more, in this report we identify a new subset of NK cells, CD11c+ HLA-DR+, reported previously in a mouse lupus model. It is essential to highlight that these NK cells with DC-like phenotype could be crucial for the development of SLE.
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Disclosure of Interest None declared