Decreased glycolysis induced dysfunction of NK cells in Henoch-Schonlein purpura patients
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RESEARCH ARTICLE
Open Access
Decreased glycolysis induced dysfunction of NK cells in Henoch-Schonlein purpura patients Wenjia Chai, Xiaolin Wang, Wei Wang, Hui Wang, Wenjun Mou and Jingang Gui*
Abstract Background: Henoch-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. Results: A 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. Conclusions: Our 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. Keywords: Henoch-Schonlein purpura, Henoch-Schonlein purpura nephritis, NK cells, Glycolysis, Metabolic reprogramming
Background Henoch-Schonlein purpura (HSP), also referred to as IgA vasculitis, is characterized by immunoglobulin A1 (IgA1)dominant immune deposits affecting small vessels [1]. The multiple manifestations of the disease include nonthrombocytopenic purpura, arthritis, gastrointestinal involvement and nephritis [2]. Among HSP nephritis (HSPN) patients, most possess a mild form of the disease, presenting with only * Correspondence: [email protected] Laboratory of Tumor Immunology, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing 100045, China
hematuria and/or low-grade proteinuria, while a few cases will develop into nephrotic syndrome or renal function impairment [2, 3]. The severity of renal involvement was proved to affect the disease prognosis greatly [4]. HSP is frequently reported to follow respiratory infections, and a variety of pathogens, such as viral and bacterial pathogens, have been implicated as triggers of the d
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