Effect of 1.25(OH)2D3 on experimental autoimmune neuritis and its mechanism

Di Nian, Zhuohan Li, Junjie Sun, Peng Shi

Article ID: 1375
Vol 5, Issue 2.1, 2021

VIEWS - 42 (Abstract) 32 (PDF)

Abstract


Objective: To study the potential therapeutic effects of active vitamin D3 (1.25(OH)2D3) in the experimental autoimmune neuritis (EAN). Methods: The EAN model was established by actively immunizing Lewis rats with synthetic P0180199 pepide and Freund’s complete adjuvant. 1.25(OH)2D3 treatment was given, weight change of rats and clinical score were analyzed. HE staining was used to detect the inflammatory cell infiltration of sciatic nerves and demyelination of sciatic nerves was observed by transmission electron microscope (TEM) at the same time. The expressions of inflammatory cytokines IL-17, IL-10, TGF-β, IFN-γ were detected by ELISA, and the expressions of Th17, Treg were examined by RT-PCR. Results: 1.25(OH)2D3 ameliorated body weight loss and myelin lesions. It decreased expressions of inflammatory cytokines IL-17, IFN-γ and RORrt while those of IL-10, TGF-β and FoxP3 were increased. Conclusions: 1.25(OH)2D3 can improve the clinical pathological changes of EAN rats, and the mechanism may be related to the changes of inflammatory cytokines. 1.25(OH)2D3 is expected to become a new strategy for the clinical treatment of GBS/EAN.


Keywords


Experimental Autoimmune Neuritis; 1.25(OH)2D3; Inflammation Cytokines; T-lymphocytes

Full Text:

PDF


References


1. Haussler MR, Whitfield GK, Kanekop I, et al. Molecular mechanisms of vitamin D action. Calcified Tissue International 2013; 92(2): 77–98.

2. Bogdanou D, Penna-Martinez M, Filmann N, et al. T-lymphocyte and glycemic status after vitamin D treatment in type 1 diabetes: A randomized controlled trial with sequential crossover. Diabetes/Metabolism Research and Reviews 2017; 33(3): e2865.

3. Chun RF, Liu PT, Modlin RL, et al. Impact of vitamin D on immune function: Lessons learned from genome wide analysis. Frontiers in Physiology 2014; 21(5): 151–165.

4. Finch SL, Rosenberg AM, Hassan V. Vitamin D and juvenile idiopathic arthritis. Pediatric Rheumatology 2018; 16: 34–50.

5. Vanherwegen AS, Gysemans C, Mathieu C. Regulation of immune function by vitamin D and its use in disease of immunity. Endocrinology and Metabolism Clinics of North America 2017; 46(4): 1061–1094.

6. Spanier JA, Nashold FE, Mayne CG, et al. Vitamin D and estrogen synergy in Vdr-expressing CD4+ T cells is essential to induce Helios+ FoxP3+ T cells and prevent autoimmune demyelinating disease. Journal of Neuroimmunology 2015; 15(286): 48–58.

7. Meehan TF, Vanhooke J, Prahl J, et al. Hypercalcemia produced by parathyroid hormone suppresses experimental autoimmune encephalomyelitis in female but not male mice. Archives of Biochemistry and Biophysics 2005; 442: 214–221.

8. Ding Y, Han R, Jiang W, et al. Programmed death ligand 1 plays a neuroprotective role in experimental autoimmune neuritis by controlling peripheral nervous system inflammation of rats. The Journal of Immunology 2016; 197(10): 3831–3840.

9. Gualdoni GA, Mayer KA, Göschl L, et al. The AMP analog AICAR modulates the Treg/Th17 axis through enhancement of fatty acid oxidation. FASEB Journal 2016; 30(11): 3800–3809.

10. Sun Y, Tian T, Gao J, et al. Metformin ameliorates the development of experimental autoimmune encephalomyelitis by regulating T helper 17 and regulatory T cells in mice. Journal of Neuroimmunology 2016; 292: 58–67.

11. Wang X, Zheng XY, Ma C, et al. Mitigated Tregs and augmented Th17 cells and cytokines are associated with severity of experimental autoimmune neuritis. Scandinavian Journal of Immunology 2014; 80(3): 180–190.

12. Joshi S, Pantalena LC, Liu XK, et al. 1,25-Dihydroxyvitamin D3 ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A. Molecular and Cellular Biology 2011; 31(17): 3653–3669.

13. Shi P, Dong W, Nian D, et al. Bifidobacterium alleviates guillain-barré syndrome by regulating the function of T17 cells. International Journal of Clinical and Experimental Medicine 2018; 11(5): 4779–4786.

14. Shi P, Qu H, Nian D, et al. Treatment of Guillain-Barré syndrome with bidobacterium infantis through regulation of T helper cells subsets. International Immunopharmacology 2018; 61: 290–296.

15. Zhou L, Wang J, Li J, et al. 1,25-Dihydroxyvitamin D3 ameliorates collagen-induced arthritis via suppression of Th17 cells through miR-124 mediated inhibition of IL-6 signaling. Frontiers in Immunology 2019; 10: 178–190.

16. Marinho A, Carvalho C, Boleixa D, et al. Vitamin D supplementation effects on FoxP3 expression in T cells and FoxP3/IL-17A ratio and clinical course in systemic lupus erythematosus patients: A study in a Portuguese cohort. Immunologic Research 2017; 65(1): 197–206.

17. Singh K, Gandhi S, Batool R. A case-control study of the association between vitamin D levels and gastric incomplete intestinal metaplasia. Nutrients 2018; 10(5): 629–637.

18. Tedeschi SK, Aranow C, Kamen DL, et al. Effect of vitamin D on serum markers of bone turnover in SLE in a randomized controlled trials. Lupus Science & Medicine 2019; 17(6): e000352.

19. Vlot MC, Boekel L, Kragt J, et al. Multiple sclerosis patients show lower bioavailable 25(OH)D and 1,25(OH)2D, but no difference in ratio of 25(OH)D/24,25(OH)2D and FGF23 concentrations. Nutrients 2019; 11(11): 2774–2789.

20. Hau CS, Shimizu T, Tada Y, et al. The vitamin D3 analog, maxacalcitol, reduces psoriasiformskin inflammation by inducing regulatory T cells and downregulating IL-23 and IL-17 production. Journal of Dermatological Science 2018; 92(2): 117–126.

21. Jeffery LE, Henley P, Marium N, et al. Decreased sensitivity to 1,25-dihydroxyvitamin D3 in T cells from the rheumatoid joint. Journal of Autoimmunity 2018; 88: 50–60.

22. Mohammadi-Kordkhayli M, Ahangar-Parvin R, Azizi SV, et al. Vitamin D modulates the expression of IL-27 and IL-33 in the central nervous system in Experimental Autoimmune Encephalomyelitis (EAE). Iranian Journal of Immunology 2015; 12(1): 35–49.

23. Speck S, Lim J, Shelake S, et al. TGF-β signaling initiated in dendritic cells instructs suppressive effects on Th17 differentiation at the site of neuroinflammation. Plos One 2014; 9(7): e102390.

24. Austin PJ, Kim CF, Perera CJ, et al. Regulatory T cells attenuate neuropathic pain following peripheral nerve injury and experimental autoimmune neuritis. Pain 2012; 153(9): 1916–1931.

25. Ahangar-Parvin R, Mohammadi-Kordkhayli M, Azizi SV, et al. The modulatory effects of vitamin D on the expression of IL-12 and TGF-β in the spinal cord and serum of mice with experimental autoimmune encephalomyelitis. Iranian Journal of Immunology 2018; 13(1): 10–22.

26. Haghmorad D, Yazdanpanah E, Tavaf MJ, et al. Prevention and treatment of experimental autoimmune encephalomyelitis induced mice with 1,25-dihydroxyvitamin D3. Neurological Research 2019; 41(10): 943–957.

27. Tone Y, Furuuchi K, Kojima Y, et al. Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer. Nature Immunology 2008; 9(2): 194–202.

28. Liu HP, Cao AT, Feng T, et al. TGF-β converts Th1 cells into Th17 cells through stimulation of Runx1 expression. European Journal of Immunology 2015; 45(4): 1010–1018.

29. Kataoka H, Yasuda S, Fukaya S, et al. Decreased expression of Runxl and lowered proportion of Foxp3+ CD25+ CD4+ regulatory T cells in systemic sclerosis. Modern Rheumatology 2015; 25(1): 90–95.




DOI: https://doi.org/10.24294/ti.v5.i2.1.1375

Refbacks

  • There are currently no refbacks.


Copyright (c) 2021 Di Nian, Zhuohan Li, Junjie Sun, Peng Shi

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

This site is licensed under a Creative Commons Attribution 4.0 International License.