Abstract
BackgroundHenoch-Schonlein purpura (HSP) is the most common systemic vasculitis of the childhood. However, its mechanisms and pathogenesis still need more exploration. Natural killer (NK) cells are innate lymphocytes, and there is a growing appreciation that cellular metabolism is important in determining the immune responsiveness of lymphocytes. Thus, we aimed to analyze the NK cells phenotype and explore the association between glucose metabolism and NK cells function in HSP patients.ResultsA total number of 64 HSP patients and 34 healthy children were included. The HSP patients were divided into two groups according to whether accompanied with nephritis or not. NK cells in HSP patients without nephritis showed a reduced frequency in peripheral blood, a down-regulated expression of activating receptors both NKp30 and NKp46, and an attenuated cytotoxic function against tumor cells. In addition, the function impairment of NK cells was shown to exacerbate in HSPN. Our data further revealed an aberrant metabolic reprogramming of NK cells in HSP patients. Upon stimulation with cytokines (IL-15, IL-12 and IL-2), NK cells from healthy controls switched to an elevated glycolysis rate to support their effector function. By contrast, the glycolysis rate of activated NK cells in HSP group was not significantly up-regulated from the resting level possibly owing to the inhibition of mTORC1.ConclusionsOur study found that HSP patients were accompanied with dysfunction of NK cells. We concluded that the dysfunction of NK cells in HSP patients was induced with a decreased glycolysis rate and suggested that metabolic reprogramming of NK cells might be a player in the pathogenesis of HSP.
Highlights
Henoch-Schonlein purpura (HSP) is the most common systemic vasculitis of the childhood
The multiple analysis indicated that the frequency and absolute count of CD56+ CD3- Natural killer (NK) cells in HSP patients were decreased compared with that in healthy controls, and further reduced in HSP nephritis (HSPN) patients (Fig. 1 a, b, c)
Following 18 h stimulation, Mammalian target of rapamycin complex1 (mTORC1) activity of HSP NK cells were significantly inhibited, and a noticeable further down-slope change in HSPN group was secured (Fig. 4e). These results indicated that the glucose uptake capacity and the glycolysis rate of activated NK cells from HSP patients were significantly decreased, which might be a consequence from the inhibition of mTORC1
Summary
Henoch-Schonlein purpura (HSP) is the most common systemic vasculitis of the childhood. Henoch-Schonlein purpura (HSP), referred to as IgA vasculitis, is characterized by immunoglobulin A1 (IgA1)dominant immune deposits affecting small vessels [1]. The diminished glycosylation of the hinge region of IgA1 in HSP patients are prone to aggregate into macromolecular complexes, which activate the pathway of complement and deposit affected organs [8, 9]. Several inflammatory cytokines, such as IL-17, IL-8, IL-6 and TGF-α, were involved in IgA elevation in HSP patients [10,11,12,13]. Immune cells such as Th1, Th2, Th17 and Treg cells participate in the progress of HSP [14,15,16], but the role of NK cells in HSP or HSPN pathogenesis were undefined
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