Interleukin-7 expression and its effect on natural killer cells in patients with multiple sclerosis

Abstract

Decreased NK cell numbers and impairment of NK cell function are reported in patients with multiple sclerosis (MS). Interleukin-7 (IL-7) is a member of the common gamma-chain (γc) cytokine superfamily that has well documented roles in lymphocyte development and homeostasis. The interleukin-7 receptor α chain (IL-7Rα) gene was identified as a top non-major histocompatibility complex-linked risk locus for MS. The objective of this study was to test biological function of IL-7/IL-7Rα on NK cells in MS patients. We observed markedly lower IL-7 levels in MS sera, and relatively higher IL-7Rα expression in NK cells of MS. Upon IL-7 stimulation, IL-7Rα on NK cells from MS patients was significantly down-regulated compared with healthy controls (HC). IL-7 induced a higher increase of IFN-γ production in CD56bright NK cells and a pronounced enhancement of cytotoxicity in NK cells from MS. IL-7 does not impact the proliferation of NK cells differently in MS and HC. In contrast, IL-7 promotes a higher survival of CD56bright NK cells in MS and inhibits their apoptosis by increasing Bcl-2 expression, but has no effect on CD56dim NK cell survival in MS. In conclusion, MS patients have lower serum IL-7 and a higher membrane IL-7Rα expression on CD56bright NK cells. The skew at the IL-7 and IL-7Rα level influences functional responsiveness of NK cells in MS.

CD56bright NK IL-7Rα expression negatively associates with HCV level, and IL-7-induced NK function is impaired during HCV and HIV infections

“…4). These results are consistent with previous literature [31,38]. There was no detectable effect on BCL-2 or Ki67 expression in the CD56 dim or CD56 neg NK cell subsets.…”

“…Previous findings demonstrate that IL-7 can promote CD56 bright NK cell IFN-g production in uninfected control subject samples and those of patients with multiple sclerosis [38]. Here, we extend these findings to determine the effect of IL-7 on NK cell IFN-g and TNF-a expression during chronic viral infection.…”

“…CD8 T cell CD127 expression is positively associated with IFNg-producing capacity in HCV-infected subjects [29,30]. IL-7 has also been shown to augment CD56 bright NK IFN-g production, with heightened effects in NK cells of multiple sclerosis patients [38]. Here, we show that IL-7 enhances NK cell IFN-g release and promotes CD56 bright NK cell IFN-g production.…”

“…Previous findings have shown that IL-7 promotes CD56 bright NK cell survival via up-regulation of BCL-2 [31] and induces cell cycling [38]. Whether this activity is altered during chronic viral infection is unknown.…”

“…Cytotoxicity is a vital antiviral NK cell effector function that can occur through multiple mechanisms. Previous studies have shown that IL-7 can enhance CD56 bright NK cell CD107a expression [38]. Therefore, we measured NK cell subset upregulation of CD107a, a degranulation marker, in purified NK cells after culture with K562 target cells, in the presence or absence of IL-7 or IFN-a.…”