Distribution of FoxP3+regulatoryT-cells in rat’spancreatic lymph nodes under streptozotocin-induced diabetes and metformin administration

Authors

  • D. A. Putilin
  • A. M. Kamyshnyi

DOI:

https://doi.org/10.14739/2310-1237.2015.1.42830

Keywords:

Diabetes mellitus, FoxP3, Metformin, Treg

Abstract

Type 1 diabetes mellitus is a T-cellmediated autoimmune disease characterized by the destruction of β-cells of the pancreas. Numerous studies have demonstrated the key role of FoxP3+ regulatory T-cells in the development of type 1 diabetes.

The aim of our study:1) to determine the expression patterns of transcription factor FoxP3 in the pancreatic lymph node cells in animal model of diabetes mellitus and 2) to assay an effect of metformin on these processes.

Methods and results.The studywas conducted on 60 male Wistar rats with streptozotocin-induced modeling diabetes with various duration of the diabetes. Within development of type 1 diabetes mellitus the number of Treg pancreatic lymph nodes has been reduced.

Conclusion.These findings demonstrate the ability of metformin to increase the number of Treg.

References

Araki, K., Ellebedy, A., & Ahmed, R. (2011). mTOR in the immune system.CurrOpinCellBiol, 23(6), 707–715.

Calderon, B., &Unanue, E. (2012). Antigen presentation events in autoimmune diabetes.CurrOpinImmunol, 24(1), 119–128. doi: 10.1016/j.coi.2011.11.005.

Ferraro, A., Socci, C., Stabilini, A., Valle, A., Monti, P., Piemonti, L., et al. (2011). Expansion of Th17 cells and functional defects in T regulatory cells are key features of the pancreatic lymph nodes in patients with type 1 diabetes. Diabetes, 60, 2903–2913.doi: 10.2337/db11-0090.

Ferraro, A., Socci, C., & Battaglia, M. (2011). Expansion of Th17 Cells and Functional Defects in T Regulatory Cells Are Key Features of the Pancreatic Lymph Nodes in Patients With Type 1 Diabetes. Diabetes, 60(11), 2903–2913. doi: 10.2337/db11-0090.

Gagnerault, M., Luan, J., Lotton, C., &Lepault, F. (2002). Pancreatic lymph nodes are required for priming of β cell reactive T cells in NOD mice. J Exp Med., 196, 369–377.doi: 10.1084/jem.20011353.

Gerriets, V., &Rathmell, J. (2012). Metabolic pathways in T cell fate and function. Trends Immunol., 33(4), 168–73. doi: 10.1016/j.it.2012.01.010.

Green, E., Choi, Y., &Flavell, R. (2002). Pancreatic lymph node-derived CD4(+)CD25(+) Treg cells: highly potent regulators of diabetes that require TRANCE-RANK signals. Immunity, 16, 183–191. doi:10.1016/S1074-7613(02)00279-0.

Gardie, D. (2011). AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. Genes Dev., 25, 1895–908.doi: 10.1101/gad.17420111.

Kole, T., Zheng, Y., Zarek. P., Matthews, K., Xiao, B., Worley, P., et al. (2009). The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity,30, 832–844. doi: 10.1016/j.immuni.2009.04.014.

Levisetti, M., Suri, A., Frederick, K., &Unanue, E. (2004). Absence of lymph nodes in NOD mice treated with lymphotoxin-β receptor immunoglobulin protects from diabetes. Diabetes, 53, 3115–3119. doi:10.2337/diabetes.53.12.3115.

MacIver, N., Michalek, R., &Rathmell, J. (2013). Metabolic regulation of T lymphocytes.Annu Rev Immunol, 31, 259–83.doi: 10.1146/annurev-immunol-032712-095956.

Michalek, R., Gerriets, V., Jacobs, S., Macintyre, A., MacIver, N., Mason, E., et al. (2011). Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol, 186, 3299–303.doi: 10.4049/jimmunol.1003613.

Nasri, H., & Rafieian-Kopaei, M. (2014). Metformin: Current knowledge. J Res Med Sci, 19(7), 658–664.

Nti, B., Markman, J., Bertera, S., Styche, A., Lakomy, R., Subbotin, V. et al. (2012). Treg cells in pancreatic lymph nodes: the possible role in diabetogenesis and beta cell regeneration in a T1D model. Cell MolImmunol, 9, 455–463. doi: 10.1038/cmi.2012.36.

Salmond, R., &Zamoyska, R. (2011). The influence of mTOR on T helper cell differentiation and dendritic cell function. Eur J Immunol,41(8), 2137–2141. doi: 10.1002/eji.201141523.

Tan, T., Xiang, Y., Chang, C., & Zhou, Z. (2014). Alteration of regulatory T cells in type 1 diabetes mellitus: a comprehensive review.Clin. Rev. Allergy Immunol., 47(2), 234–243. doi: 10.1007/s12016-014-8440-0.

Tonkin, D., & Haskins, K. (2009). Regulatory Tcells enter the pancreas during suppression of type 1 diabetes and inhibit effector Tcells and macrophages in a TGF-beta-dependent manner.Eur J Immunol, 39, 1313–1322.doi: 10.1002/eji.200838916.

Willcox,A., Richardson, S., Bone, A., Foulis, A., & Morgan, N. (2009) Analysis of islet inflammation in human type 1 diabetes.ClinExpImmunol, 155,173–181.doi: 10.1111/j.1365-2249.2008.03860.x.

Yaochite, J., Caliari-Oliveira, C., & Davanso, M. (2013). Dynamic changes of the Th17/Tc17 and regulatory T cell populations interfere in the experimental autoimmune diabetes pathogenesis.Immunobiology, 218(3), 338–52.doi: 10.1016/j.imbio.2012.05.010.

Zdravkovic, N., Shahin, A., Arsenijevic, N., Lukic, M., &Mensah-Brown, E. (2009). Regulatory T cells and ST2 signaling control diabetes induction with multiple low doses of streptozotocin.MolImmunol, 47(1), 28–36. doi: 10.1016/j.molimm.2008.12.023.

Downloads

How to Cite

1.
Putilin DA, Kamyshnyi AM. Distribution of FoxP3+regulatoryT-cells in rat’spancreatic lymph nodes under streptozotocin-induced diabetes and metformin administration. Pathologia [Internet]. 2015May19 [cited 2024Nov.24];(1). Available from: http://pat.zsmu.edu.ua/article/view/42830

Issue

Section

Original research