Interleukin-7 Expression and its Effect on Natural Killer Cells in Patients With Multiple Sclerosis
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 (Î³c) cytokine superfamily that has well documented roles in lymphocyte development and homeostasis. The interleukin-7 receptor Î± chain (IL-7RÎ±) 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-7RÎ± on NK cells in MS patients. We observed markedly lower IL-7 levels in MS sera, and relatively higher IL-7RÎ± expression in NK cells of MS. Upon IL-7 stimulation, IL-7RÎ± on NK cells from MS patients was significantly down-regulated compared with healthy controls (HCs). IL-7 induced a higher increase of IFN-Î³ 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-7RÎ± expression on CD56bright NK cells. The skew at the IL-7 and IL-7RÎ± level influences functional responsiveness of NK cells in MS.
Medical Subject Headings
Journal of Neuroimmunology
Digital Object Identifier (DOI)
Su, Ning; Shi, Samuel X.; Zhu, Xiaodong; Borazanci, Aimee; Shi, Fu-Dong; and Gan, Yan, "Interleukin-7 Expression and its Effect on Natural Killer Cells in Patients With Multiple Sclerosis" (2014). Neurology. 26.