Downregulation of Immunosuppressive Molecules, PD-1 and PD-L1 but not PD-L2, in the Patients with Multiple Sclerosis

被引:3
作者
Javan, Mohammad Reza [1 ,2 ]
Aslani, Saeed [3 ]
Zamani, Mohammad Reza [4 ]
Rostamnejad, Javad [5 ]
Asadi, Milad [6 ]
Farhoodi, Mahdi [7 ]
Nicknam, Mohammad Hossein [3 ,8 ]
机构
[1] Zabol Univ Med Sci, Dept Immunol, Fac Med, Zabol, Iran
[2] Tabriz Univ Med Sci, Sch Med, Dept Immunol, Tabriz, Iran
[3] Univ Tehran Med Sci, Sch Med, Dept Immunol, Tehran, Iran
[4] USERN, Network Immun Infect Autoimmun & Malignancy NIIMA, Tehran, Iran
[5] Shahid Beheshti Univ Med Sci, Sch Med, Dept Genet, Tehran, Iran
[6] Tabriz Univ Med Sci, Immunol Res Ctr, Tabriz, Iran
[7] Tabriz Univ Med Sci, Dept Neurol, Neurosci Res Ctr, Tabriz, Iran
[8] Univ Tehran Med Sci, Mol Immunol Res Ctr, Tehran, Iran
关键词
Gene expression; Multiple sclerosis; Programmed cell death 1 receptor; Programmed cell death 1 ligand 1 protein; Programmed cell death 1 ligand 2 protein; T-CELL-ACTIVATION; RESPONSES; AUTOIMMUNITY; PATHOGENESIS; POLYMORPHISM; PD-1/PD-L1; DIAGNOSIS; FAMILY;
D O I
暂无
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Programmed cell death-1 (PD-1) and its ligands, PD-L1 and PD-L2, have been regarded as important immune system regulatory molecules. The aberrant expression of the molecules has been related to several autoimmune disorders. This study is aimed to assess the mRNA expression level of PD-1, PD-L1, and PD-L2 molecules in the peripheral blood mononuclear mells (PBMCs) from multiple sclerosis (MS) patients. PBMCs were isolated from the whole blood of 50 MS and 50 healthy individuals. Total RNA content of the leukocytes was extracted. Then, cDNA was synthesized from the extracted RNA. Afterwards, quantitative analysis of PD-1, PD-L1 and PD-L2 was carried out through Real Time PCR using the TaqMan gene expression assays. Relative expression of PD-1 and PD-L1 in PBMCs from MS patients was significantly lower compared with the healthy control group (p=0.003 and 0.012, respectively). However, no significant difference was observed in the expression level of PD-L2 between patients and healthy individuals. Relative expression of PD-1 correlated with expanded disability status scale score (EDSS) of the patients (r=-0.763, p=0.008). Downregulation of the immunosuppressive molecules, PD-1 and PD-L1, may imply that over-activation of immune cells in multiple sclerosis occurs through signaling dysfunction of these molecules and PD-L2 plays no important role in this context.
引用
收藏
页码:296 / 302
页数:7
相关论文
共 25 条
[1]   The autoimmune tautology [J].
Anaya, Juan-Manuel .
ARTHRITIS RESEARCH & THERAPY, 2010, 12 (06)
[2]   PD-1/PD-L1, but not PD-1/PD-L2, interactions regulate the severity of experimental autoimmune encephalomyelitis [J].
Carter, Laura L. ;
Leach, Michael W. ;
Azoitei, Mihai L. ;
Cui, Junqing ;
Pelker, Jeffrey W. ;
Jussif, Jason ;
Benoit, Steve ;
Ireland, Gretchen ;
Luxenberg, Deborah ;
Askew, G. Roger ;
Milarski, Kim L. ;
Groves, Christopher ;
Brown, Tom ;
Carito, Brenda A. ;
Percival, Karen ;
Carreno, Beatriz M. ;
Collins, Mary ;
Marusic, Suzana .
JOURNAL OF NEUROIMMUNOLOGY, 2007, 182 (1-2) :124-134
[3]   Molecular mechanisms of T cell co-stimulation and co-inhibition [J].
Chen, Lieping ;
Flies, Dallas B. .
NATURE REVIEWS IMMUNOLOGY, 2013, 13 (04) :227-242
[4]   Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity [J].
Chen, LP .
NATURE REVIEWS IMMUNOLOGY, 2004, 4 (05) :336-347
[5]   Multiple sclerosis [J].
Compston, A ;
Coles, A .
LANCET, 2002, 359 (9313) :1221-1231
[6]   Costimulating aberrant T cell responses by B7-H1 autoantibodies in rheumatoid arthritis [J].
Dong, HD ;
Strome, SE ;
Matteson, EL ;
Moder, KG ;
Flies, DB ;
Zhu, GF ;
Tamura, H ;
Driscoll, CLW ;
Chen, LP .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 111 (03) :363-370
[7]   Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation [J].
Freeman, GJ ;
Long, AJ ;
Iwai, Y ;
Bourque, K ;
Chernova, T ;
Nishimura, H ;
Fitz, LJ ;
Malenkovich, N ;
Okazaki, T ;
Byrne, MC ;
Horton, HF ;
Fouser, L ;
Carter, L ;
Ling, V ;
Bowman, MR ;
Carreno, BM ;
Collins, M ;
Wood, CR ;
Honjo, T .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (07) :1027-1034
[8]   Recent insights into the role of the PD-1/PD-L1 pathway in immunological tolerance and autoimmunity [J].
Gianchecchi, Elena ;
Delfino, Domenico Vittorio ;
Fierabracci, Alessandra .
AUTOIMMUNITY REVIEWS, 2013, 12 (11) :1091-1100
[9]  
Goldenberg Marvin M, 2012, P T, V37, P175
[10]   Role of the innate and adaptive immune responses in the course of multiple sclerosis [J].
Hemmer, Bernhard ;
Kerschensteiner, Martin ;
Korn, Thomas .
LANCET NEUROLOGY, 2015, 14 (04) :406-419