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

• Serum IL-7 level is decreased and expression of IL-7Rα (CD127) on NK cells is increased in MS patients.
• IL-7 stimulation leads to higher increase in cytokine production by CD56bright NK cells and cytotoxicity in NK cells of MS patients.
• IL-7 induced proliferation in NK cells does not differ between MS patients and healthy controls.
• IL-7 promotes an increased survival in CD56bright NK cells of MS patients by up-regulating Bcl-2 expression.

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 (HCs). 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 did not impact the proliferation of NK cells differently in MS and HC. In contrast, IL-7 promoted a higher survival of CD56bright NK cells in MS and inhibited their apoptosis by increasing Bcl-2 expression, but had 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.