Therapeutic potential of atorvastatin-modified dendritic cells in experimental autoimmune neuritis by decreased Th1/Th17 cytokines and up-regulated T regulatory cells and NKR-P1(+) cells

Hua Xu; Xiao-Li Li; Long-Tao Yue; Heng Li; Min Zhang; Shan Wang; Cong-Cong Wang; Rui-Sheng Duan

doi:10.1016/j.jneuroim.2014.02.002

Therapeutic potential of atorvastatin-modified dendritic cells in experimental autoimmune neuritis by decreased Th1/Th17 cytokines and up-regulated T regulatory cells and NKR-P1(+) cells

J Neuroimmunol. 2014 Apr 15;269(1-2):28-37. doi: 10.1016/j.jneuroim.2014.02.002. Epub 2014 Feb 12.

Authors

Hua Xu¹, Xiao-Li Li², Long-Tao Yue³, Heng Li², Min Zhang², Shan Wang², Cong-Cong Wang², Rui-Sheng Duan⁴

Affiliations

¹ Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China; Taian City Central Hospital, Taian 271000, PR China.
² Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
³ Central Laboratory, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
⁴ Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China. Electronic address: ruisheng_duan@yahoo.com.

PMID: 24565076
DOI: 10.1016/j.jneuroim.2014.02.002

Abstract

Statins have pleiotropic effects which include anti-inflammatory and immunomodulatory effects. In the present study, dendritic cells treated with atorvastatin (statin-DCs) could be induced into tolerogenic DCs. Administration of these tolerogenic DCs ameliorated clinical symptoms in experimental autoimmune neuritis (EAN), which was associated with reduced number of inflammatory cells in sciatic nerves, inhibited CD4(+) T cells proliferation, down-regulated expression of co-stimulatory molecules (CD80 and CD86) and MHC class II, decreased levels of IFN-γ, TNF-α and IL-17A, increased number of NKR-P1(+) cells (including NK and NKT cells), up-regulated number of Treg cells in lymph node MNC as well as increased Foxp3 expression in the thymus. These data indicated that statin-DCs could develop as a new therapeutic strategy to GBS in the future.

Keywords: Cytokines; Dendritic cells; Experimental autoimmune neuritis; NKR-P1(+) cells; Statins.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Atorvastatin
Cattle
Cytokines / metabolism
Dendritic Cells / drug effects
Dendritic Cells / immunology
Dendritic Cells / metabolism*
Female
Heptanoic Acids / pharmacology
Heptanoic Acids / therapeutic use*
NK Cell Lectin-Like Receptor Subfamily B / immunology
NK Cell Lectin-Like Receptor Subfamily B / metabolism*
Neuritis, Autoimmune, Experimental / drug therapy
Neuritis, Autoimmune, Experimental / immunology
Neuritis, Autoimmune, Experimental / metabolism*
Pyrroles / pharmacology
Pyrroles / therapeutic use*
Rats
Rats, Inbred Lew
T-Lymphocytes, Regulatory / drug effects
T-Lymphocytes, Regulatory / immunology
T-Lymphocytes, Regulatory / metabolism
Th1 Cells / drug effects
Th1 Cells / immunology
Th1 Cells / metabolism*
Th17 Cells / drug effects
Th17 Cells / immunology
Th17 Cells / metabolism*
Up-Regulation / drug effects
Up-Regulation / physiology

Substances

Cytokines
Heptanoic Acids
KLRB1 protein, human
NK Cell Lectin-Like Receptor Subfamily B
Pyrroles
Atorvastatin