Abstract
The increased incidence of systemic lupus erythematosus (SLE) in recent decades might be related to changes in modern dietary habits. Since sodium chloride (NaCl) promotes pathogenic T cell responses, we hypothesize that excessive salt intake contributes to the increased incidence of autoimmune diseases, including SLE. Given the importance of dendritic cells (DCs) in the pathogenesis of SLE, we explored the influence of an excessive sodium chloride diet on DCs in a murine SLE model. We used an induced lupus model in which bone marrow-derived dendritic cells (BMDCs) were incubated with activated lymphocyte-derived DNA (ALD-DNA) and transferred into C57BL/6 recipient mice. We observed that a high-salt diet (HSD) markedly exacerbated lupus progression, which was accompanied by increased DC activation. NaCl treatment also stimulated the maturation, activation and antigen-presenting ability of DCs in vitro. Pretreatment of BMDCs with NaCl also exacerbated BMDC-ALD-DNA-induced lupus. These mice had increased production of autoantibodies and proinflammatory cytokines, more pronounced splenomegaly and lymphadenopathy, and enhanced pathological renal lesions. The p38 MAPK–STAT1 pathway played an important role in NaCl-induced DC immune activities. Taken together, our results demonstrate that HSD intake promotes immune activation of DCs through the p38 MAPK–STAT1 signaling pathway and exacerbates the features of SLE. Thus, changes in diet may provide a novel strategy for the prevention or amelioration of lupus or other autoimmune diseases.
Highlights
Acid-Schiff (PAS), and periodic acid-silver methenamine (PASM) DNA and injected these cells into CD45.2 C57BL/6 mice; at 14 days staining of lupus mouse kidney paraffin sections, severe renal after injection, we found that the donor dendritic cells that had pathological lesions were more pronounced in kidneys from high-salt diet (HSD) been incubated with activated lymphocyte-derived DNA (ALD-DNA) exerted higher activation than lupus mice than in those from normal-salt diet (NSD) lupus mice (Fig. 1c)
Since p38 MAPK kinase is required for interferon-induced STAT1 serine phosphorylation and transcriptional activation,[78] we examined the p38 MAPK and STAT1 protein levels in bone marrow-derived dendritic cells (BMDCs) and found that p38 MAPK and STAT1 were significantly increased in dendritic cells that were treated with sodium chloride; otherwise, the ratio of phospho-STAT1/total STAT1 showed no BMDC-Blank BMDC-NaCl P value
Since the influence of sodium chloride on dendritic cells has not been fully explored, a major investigative effort of the present study focused on the specific effect of sodium chloride on dendritic cells using a lupus model; this approach was supported by the results of our previous study that used BMDCs that were incubated with ALDDNA and transferred to mice by tail vein injection.[50,56]
Summary
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that is characterized by increased production of various autoantibodies against autoantigens and mainly affects women of childbearing age.[1,2,3,4] the etiology of SLE is still incompletely understood, genetic susceptibility, hormonal modulation, environmental factors, and gut microbes related to diet are involved in the development of SLE.[5,6,7,8] Abnormalities in the adaptive immune system, including B and T cells and the production of pathogenic autoantibodies,[9,10,11,12,13,14] and components of the innate immune system, including dendritic cells and complement, all participate in the occurrence and development of SLE.[15,16,17,18] SLE pathogenic inflammatory T cells contribute to cytokine generation and help abnormal B cells produce autoantibodies.[19] Autoantibodies and complement deposition in kidneys and in other organs cause irreversible damage.[20,21,22] the treatment of lupus remains unsatisfactory,[23,24,25,26] even with some of the newer biologics.[27] Approaches to modifying diet may have the potential to significantly improve disease management
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