| First Author | Suárez-Fueyo A | Year | 2018 |
| Journal | J Immunol | Volume | 200 |
| Issue | 9 | Pages | 3077-3086 |
| PubMed ID | 29602774 | Mgi Jnum | J:261494 |
| Mgi Id | MGI:6155550 | Doi | 10.4049/jimmunol.1700588 |
| Citation | Suarez-Fueyo A, et al. (2018) Downregulation of CD3zeta in NK Cells from Systemic Lupus Erythematosus Patients Confers a Proinflammatory Phenotype. J Immunol 200(9):3077-3086 |
| abstractText | Cytotoxic function and cytokine profile of NK cells are compromised in patients with systemic lupus erythematosus (SLE). CD3zeta, an important molecule for NK cell activation, is downregulated in SLE T cells and contributes to their altered function. However, little is known about the role of CD3zeta in SLE NK cells. We studied CD3zeta levels and its contribution to cytotoxic, degranulation, and cytokine production capacity of NK cells from patients with SLE. Furthermore, we studied the human NK cell line, NKL, in which manipulation of CD3zeta levels was achieved using small interfering RNA and NK cells from Rag2 mice deficient in CD3zeta. We found reduced CD3zeta expression in NK cells from SLE patients independent of disease activity. Downregulation of CD3zeta expression in NK cells is mediated, at least in part, by Caspase 3, the activity of which is higher in NK cells from patients with SLE compared with NK cells from healthy donors. CD3zeta levels correlated inversely with natural cytotoxicity and the percentage of cells capable of producing the proinflammatory cytokines IFN-gamma and TNF. In contrast, CD3zeta levels showed a direct correlation with levels of Ab-dependent cellular cytotoxicity. Experiments performed in CD3zeta-silenced NKL and CD3zeta-deficient NK cells from Rag2 mice confirmed the dependence of NK cell function on CD3zeta levels. Our results demonstrate a differential role for CD3zeta in natural cytotoxicity and Ab-dependent cellular cytotoxicity. We conclude that downregulated CD3zeta confers a proinflammatory phenotype to SLE NK cells and contributes to their altered function in patients with SLE. |
