Elevated Levels of T-helper 17-associated Cytokines in Diabetes Type I Patients: Indicators for Following the Course of Disease

被引:38
作者
Baharlou, Rasoul [1 ]
Ahmadi-Vasmehjani, Abbas [1 ]
Davami, Mohammad Hasan [1 ]
Faraji, Fatemeh [1 ]
Atashzar, Mohammd Reza [1 ]
Karimipour, Firoozeh [2 ]
Sadeghi, Alireza [3 ]
Asadi, Mohammad-Ali [4 ]
Khoubyari, Mahshid [4 ]
机构
[1] Jahrom Univ Med Sci, Sch Med, Dept Immunol & Microbiol, Motahari Blvd, Jahrom, Iran
[2] Jahrom Univ Med Sci, Sch Nursing, Dept Nursing, Jahrom, Iran
[3] Jahrom Univ Med Sci, Sch Med, Dept Biochem, Jahrom, Iran
[4] Jahrom Univ Med Sci, Sch Med, Dept Student Res Comm, Jahrom, Iran
关键词
Diabetes type 1; Interferon gamma; Interleukin-17; Interleukin-21; Interleukin-27; transforming growth factor beta; PANCREATIC BETA-CELLS; TH17; CELLS; RETINOIC ACID; AUTOIMMUNITY; INTERLEUKIN-27; INFLAMMATION; IL-27; DIFFERENTIATION; ACTIVATION; EXPRESSION;
D O I
10.1080/08820139.2016.1197243
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: Type 1 diabetes (T1D) is thought to involve chronic inflammation, which is manifested by the activation and expression of different inflammatory mediators. Th1- and Th17-associated cytokines are factors that have been shown to exert profound pro-inflammatory activities and have been implicated in the pathogenesis of T1D in mice and humans.Objectives: Therefore, the aim of this case control study was to determine the serum level of IL-17, IL-21, IL-27, transforming growth factor beta (TGF-), and IFN- and their reciprocal relationship in Iranian T1D patients.Patients and Methods: Blood samples were collected from 48 T1D patients and 49 healthy individuals with no history of malignancies or autoimmune disorders based on simple sampling. The serum levels of IL-17, IL-21, IL-27, TGF-, and IFN- were measured by the enzyme linked immunosorbent assay (ELISA).Results: The serum levels of IL-17 and IL-21 were significantly higher in T1D patients compared to the healthy individuals (p = 0.005 and 0.01, respectively), but interestingly, the opposite was the case for IL-27 (p < 0.0001). However, there were no significant differences in TGF- and IFN- between both groups. In addition, IL-17/IFN- and IL-17/IL-27 ratios were higher in patients compared to the control group.Conclusions: Our results indicated dominant Th17-associated IL-17, suggesting a shift from the Treg and Th1 phenotypes toward the Th17 phenotype. Therefore, it can promote inflammation in cells in T1D. In addition, it suggests the role of Th17 and Th17/Th1 ratios as a potential contributor to cells destruction and the Th17/Th1 response ratio may provide a novel biomarker for rapid T1D diagnosis before the destruction of cells and progression of the disease to the clinical end stages.
引用
收藏
页码:641 / 651
页数:11
相关论文
共 38 条
[1]   Peripheral and Islet Interleukin-17 Pathway Activation Characterizes Human Autoimmune Diabetes and Promotes Cytokine-Mediated β-Cell Death [J].
Arif, Sefina ;
Moore, Fabrice ;
Marks, Katherine ;
Bouckenooghe, Thomas ;
Dayan, Colin M. ;
Planas, Raquel ;
Vives-Pi, Marta ;
Powrie, Jake ;
Tree, Timothy ;
Marchetti, Piero ;
Huang, Guo Cai ;
Gurzov, Esteban N. ;
Pujol-Borrell, Ricardo ;
Eizirik, Decio L. ;
Peakman, Mark .
DIABETES, 2011, 60 (08) :2112-2119
[2]   Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells [J].
Batten, Marcel ;
Li, Ji ;
Yi, Sothy ;
Kljavin, Noelyn M. ;
Danilenko, Dimitry M. ;
Lucas, Sophie ;
Lee, James ;
de Sauvage, Frederic J. ;
Ghilardi, Nico .
NATURE IMMUNOLOGY, 2006, 7 (09) :929-936
[3]   Isolation and Th17 Differentiation of Naive CD4 T Lymphocytes [J].
Bedoya, Simone K. ;
Wilson, Tenisha D. ;
Collins, Erin L. ;
Lau, Kenneth ;
Larkin, Joseph .
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2013, (79)
[4]   TGF-β Induces IL-9 Production from Human Th17 Cells [J].
Beriou, Gaelle ;
Bradshaw, Elizabeth M. ;
Lozano, Ester ;
Costantino, Cristina M. ;
Hastings, William D. ;
Orban, Tihamer ;
Elyaman, Wassim ;
Khoury, Samia J. ;
Kuchroo, Vijay K. ;
Baecher-Allan, Clare ;
Hafler, David A. .
JOURNAL OF IMMUNOLOGY, 2010, 185 (01) :46-54
[5]   Monocytes from Patients with Type 1 Diabetes Spontaneously Secrete Proinflammatory Cytokines Inducing Th17 Cells [J].
Bradshaw, Elizabeth M. ;
Raddassi, Khadir ;
Elyaman, Wassim ;
Orban, Tihamer ;
Gottlieb, Peter A. ;
Kent, Sally C. ;
Hafler, David A. .
JOURNAL OF IMMUNOLOGY, 2009, 183 (07) :4432-4439
[6]   Prevention versus intervention of type 1 diabetes [J].
Brooks-Worrell, Barbara ;
Palmer, Jerry P. .
CLINICAL IMMUNOLOGY, 2013, 149 (03) :332-338
[7]   Retinoic Acid Is Essential for Th1 Cell Lineage Stability and Prevents Transition to a Th17 Cell Program [J].
Brown, Chrysothemis C. ;
Esterhazy, Daria ;
Sarde, Aurelien ;
London, Mariya ;
Pullabhatla, Venu ;
Osma-Garcia, Ines ;
al-Bader, Raya ;
Ortiz, Carla ;
Elgueta, Raul ;
Arno, Matthew ;
de Rinaldis, Emanuele ;
Mucida, Daniel ;
Lord, Graham M. ;
Noelle, Randolph J. .
IMMUNITY, 2015, 42 (03) :499-511
[8]   IL-27 induces a Th1 immune response and susceptibility to experimental arthritis [J].
Cao, Yanxia ;
Doodes, Paul D. ;
Glant, Tibor T. ;
Finnegan, Alison .
JOURNAL OF IMMUNOLOGY, 2008, 180 (02) :922-930
[9]   IL-21 promotes differentiation of naive CD8 T cells to a unique effector phenotype [J].
Casey, Kerry A. ;
Mescher, Matthew F. .
JOURNAL OF IMMUNOLOGY, 2007, 178 (12) :7640-7648
[10]   Induction of autoimmune diabetes in non-obese diabetic mice requires interleukin-21-dependent activation of autoreactive CD8+ T cells [J].
Chen, X. -L. ;
Bobbala, D. ;
Rodriguez, G. M. ;
Mayhue, M. ;
Chen, Y. -G. ;
Ilangumaran, S. ;
Ramanathan, S. .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2013, 173 (02) :184-194