High-salt diet inhibits maturation and killing function of NK cells in mice

Hongyun TAO; Shiwen TONG; Wenwei YIN

doi:10.16016/j.2097-0927.202110039

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High-salt diet inhibits maturation and killing function of NK cells in mice

Basic Medicine | 更新时间：2026-01-09

- High-salt diet inhibits maturation and killing function of NK cells in mice
- Journal of Army Medical University Vol. 44, Issue 9, Pages: 882-890(2022)
- 作者机构：
  
  400010 重庆，重庆医科大学附属第二医院感染科，病毒性肝炎研究所
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81770570);the Basic Research and Frontier Exploration Project of Yuzhong District, Chongqing(030)
- DOI：10.16016/j.2097-0927.202110039
  CLC： R151.1;R392.12
- Received：10 October 2021，
  
  Revised：2021-12-07，
  
  Published：15 May 2022
- 稿件说明：
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Hongyun TAO, Shiwen TONG, Wenwei YIN. High-salt diet inhibits maturation and killing function of NK cells in mice[J]. Journal of Army Medical University, 2022, 44(9): 882-890.
DOI：

Hongyun TAO, Shiwen TONG, Wenwei YIN. High-salt diet inhibits maturation and killing function of NK cells in mice[J]. Journal of Army Medical University, 2022, 44(9): 882-890. DOI： 10.16016/j.2097-0927.202110039.

摘要

目的

探究高盐饮食对小鼠自然杀伤(natural killer，NK)细胞成熟和功能的影响。

方法

3~4周龄雄性C57BL/6J小鼠(体质量约9 g)分为正常盐饮食(normal-salt diet，NSD)组(给予普通饲料及高压灭菌水喂养)和高盐饮食(high-salt diet，HSD)组(给予含4% NaCl高盐饲料及含1% NaCl高压灭菌水喂养)。采用CD27和CD11b的表达界定NK细胞成熟亚群，CD69标记细胞的早期活化，流式细胞术分析两组小鼠NK细胞亚群分布和活化水平；采用polyI: C体内处理18 h和体外佛波酯/离子霉素刺激4 h，流式细胞术检测两组小鼠NK细胞IFN-γ产生水平；通过YAC-1体内杀伤实验，流式细胞术评估两组小鼠NK细胞的细胞毒作用。

结果

高盐饮食不影响肝脏﹑脾脏﹑骨髓和外周血NK细胞比例，但抑制肝脏、脾脏NK细胞CD69表达(

0.01)。高盐饮食组小鼠较正常盐饮食组小鼠肝、脾、骨髓中未成熟的NK细胞(CD27

CD11b

)比例增加(

0.05)，而成熟的M1 NK细胞亚群(CD27

CD11b

)比例降低(

0.05)，DX5

NK1.1

成熟NK细胞比例也降低(

0.05)，表明高盐饮食抑制NK细胞成熟。高盐饮食组小鼠NK细胞IFN-γ的表达低于正常盐饮食组小鼠(

0.01)，提示高盐饮食抑制NK细胞功能。体内杀伤实验表明，高盐饮食组小鼠腹腔剩余YAC-1细胞百分比和绝对数升高(

0.01)，提示高盐饮食抑制NK细胞的细胞毒作用。

结论

高盐饮食抑制NK细胞成熟，抑制NK细胞的活化和功能。

Abstract

Objective

To investigate the effects of high-salt diet on the maturation and function of NK cells.

Methods

Mouse models of normal salt diet (NSD) and high salt diet (HSD) were established by feeding food and drinking water with different salt content. The expression of CD27 and CD11b was used to define the NK cell maturation subsets

and the early activation of cells was labeled by CD69. Flow cytometry was employed to analyze the distribution of NK cell subsets and activation in NSD and HSD mice. The IFN-γ production level of NK cells from mice treated with polyI: C for 18 h

in vivo

and stimulated with PMA/Ionomycin for 4 h

in vitro

was detected by flow cytometry. Cytotoxic activity of NK cells was determined through the YAC-1 killing experiment

in vivo

Results

HSD showed no effect on the percentage of NK cells in the liver

spleen

bone marrow and peripheral blood

but inhibited the expression of CD69 in liver and spleen NK cells (

0.01). The percentage of immature NK cells (CD27

CD11b

) subsets was significantly higher in the liver

spleen and bone marrow from HSD mice when compared to those in NSD mice (

0.05)

while the percentage of mature M1 NK cell subsets (CD27

CD11b

) as well as DX5

NK1.1

mature NK cells were markedly lower in HSD mice (

0.05)

suggesting that HSD inhibits the maturation of NK cells. The expression of IFN-γ in NK cells of HSD mice was lower than that of NSD mice (

0.01)

indicating that HSD inhibited NK cell function. Moreover

YAC-1

in vivo

killing experiment showed that the percentage and absolute number of residual YAC-1 cells in the abdominal cavity of HSD mice were higher than those of NSD mice (

0.01)

indicating that HSD inhibited the cytotoxicity of NK cells.

Conclusion

HSD inhibits the maturation of NK cells as well as the activation and function of NK cells.

关键词

Keywords

references

POWLES J, FAHIMI S, MICHA R, et al . Global, regional and national sodium intakes in 1990 and 2010: a systematic analysis of 24 h urinary sodium excretion and dietary surveys worldwide[J ] . BMJ Open, 2013, 3(12): e003733. DOI: 10.1136/bmjopen-2013-003733.

HE F J, TAN M, MA Y, et al . Salt reduction to prevent hypertension and cardiovascular disease: JACC state-of-the-art review[J ] . J Am Coll Cardiol, 2020, 75(6): 632-647. DOI: 10.1016/j.jacc.2019.11.055.

LANASPA M A, KUWABARA M, ANDRES-HERNANDO A, et al . High salt intake causes leptin resistance and obesity in mice by stimulating endogenous fructose production and metabolism[J ] . Proc Natl Acad Sci USA, 2018, 115(12): 3138-3143. DOI: 10.1073/pnas.1713837115.

KLEINEWIETFELD M, MANZEL A, TITZE J, et al . Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells[J ] . Nature, 2013, 496(7446): 518-522. DOI: 10.1038/nature11868.

MATTHIAS J, MAUL J, NOSTER R, et al . Sodium chloride is an ionic checkpoint for human T H 2 cells and shapes the atopic skin microenvironment[J ] . Sci Transl Med, 2019, 11(480): eaau0683. DOI: 10.1126/scitranslmed.aau0683..

JOBIN K, STUMPF N E, SCHWAB S, et al . A high-salt diet compromises antibacterial neutrophil responses through hormonal perturbation[J ] . Sci Transl Med, 2020, 12(536): eaay3850. DOI: 10.1126/scitranslmed.aay3850.

HUCKE S, ESCHBORN M, LIEBMANN M, et al . Sodium chloride promotes pro-inflammatory macrophage polarization thereby aggravating CNS autoimmunity[J ] . J Autoimmun, 2016, 67: 90-101. DOI: 10.1016/j.jaut.2015.11.001.

ZHANG W C, ZHENG X J, DU L J, et al . High salt primes a specific activation state of macrophages, M(Na)[J ] . Cell Res, 2015, 25(8): 893-910. DOI: 10.1038/cr.2015.87.

XIAO Z X, HU X, ZHANG X, et al . High salt diet accelerates the progression of murine lupus through dendritic cells via the p38 MAPK and STAT1 signaling pathways[J ] . Signal Transduct Target Ther, 2020, 5(1): 34. DOI: 10.1038/s41392-020-0139-5.

VIVIER E, TOMASELLO E, BARATIN M, et al . Functions of natural killer cells[J ] . Nat Immunol, 2008, 9(5): 503-510. DOI: 10.1038/ni1582.

HABIF G, CRINIER A, ANDRÉ P, et al . Targeting natural killer cells in solid tumors[J ] . Cell Mol Immunol, 2019, 16(5): 415-422. DOI: 10.1038/s41423-019-0224-2.

CHIOSSONE L, CHAIX J, FUSERI N, et al . Maturation of mouse NK cells is a 4-stage developmental program[J ] . Blood, 2009, 113(22): 5488-5496. DOI: 10.1182/blood-2008-10-187179.

HE J, WHELTON P K, APPEL L J, et al . Long-term effects of weight loss and dietary sodium reduction on incidence of hypertension[J ] . Hypertension, 2000, 35(2): 544-549. DOI: 10.1161/01.hyp.35.2.544.

COOK N R, CUTLER J A, OBARZANEK E, et al . Long term effects of dietary sodium reduction on cardiovascular disease outcomes: observational follow-up of the trials of hypertension prevention (TOHP)[J ] . BMJ, 2007, 334(7599): 885. DOI: 10.1136/bmj.39147.604896.55.

WEI Y, LU C, CHEN J, et al . High salt diet stimulates gut Th17 response and exacerbates TNBS-induced colitis in mice[J ] . Oncotarget, 2017, 8(1): 70-82. DOI: 10.18632/oncotarget.13783.

MACHNIK A, NEUHOFER W, JANTSCH J, et al . Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism[J ] . Nat Med, 2009, 15(5): 545-552. DOI: 10.1038/nm.1960.

GO W Y, LIU X B, ROTI M A, et al . NFAT5/TonEBP mutant mice define osmotic stress as a critical feature of the lymphoid microenvironment[J ] . Proc Natl Acad Sci USA, 2004, 101(29): 10673-10678. DOI: 10.1073/pnas.0403139101.

JANTSCH J, SCHATZ V, FRIEDRICH D, et al . Cutaneous na+ storage strengthens the antimicrobial barrier function of the skin and boosts macrophage-driven host defense[J ] . Cell Metab, 2015, 21(3): 493-501. DOI: 10.1016/j.cmet.2015.02.003.

HAYAKAWA Y, SMYTH M J. CD27 dissects mature NK cells into two subsets with distinct responsiveness and migratory capacity[J]. J Immunol, 2006, 176(3): 1517-1524. DOI: 10.4049/jimmunol.176.3.1517.

RIZVI Z A, DALAL R, SADHU S, et al . High-salt diet mediates interplay between NK cells and gut microbiota to induce potent tumor immunity[J ] . Sci Adv, 2021, 7(37): eabg5016. DOI: 10.1126/sciadv.abg5016.

HE W, XU J, MU R, et al . High-salt diet inhibits tumour growth in mice via regulating myeloid-derived suppressor cell differentiation[J ] . Nat Commun, 2020, 11(1): 1732. DOI: 10.1038/s41467-020-15524-1.

ALLU A S, TIRIVEEDHI V. Cancer salt nostalgia[J]. Cells, 2021, 10(6): 1285. DOI: 10.3390/cells10061285.

AMARA S, WHALEN M, TIRIVEEDHI V. High salt induces anti-inflammatory MΦ2-like phenotype in peripheral macrophages[J]. Biochem Biophys Rep, 2016, 7: 1-9. DOI: 10.1016/j.bbrep.2016.05.009.

TANG P M, ZHOU S, MENG X M, et al . Smad3 promotes cancer progression by inhibiting E4BP 4 -mediated NK cell development[J ] . Nat Commun, 2017, 8: 14677. DOI: 10.1038/ncomms14677..

MARCOE J P, LIM J R, SCHAUBERT K L, et al . TGF-β is responsible for NK cell immaturity during ontogeny and increased susceptibility to infection during mouse infancy[J ] . Nat Immunol, 2012, 13(9): 843-850. DOI:10.1038/ni.2388.

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