Natural and induced immunization against CCL20 ameliorate experimental autoimmune encephalitis and may confer protection against multiple sclerosis

被引:8
作者
Abraham, Michal [2 ]
Karni, Arnon [3 ,4 ]
Mausner-Fainberg, Karin [3 ]
Weiss, Ido D. [1 ]
Peled, Amnon [1 ,2 ]
机构
[1] Hebrew Univ Hosp, Goldyne Savad Inst Gene Therapy, Jerusalem, Israel
[2] Biokine Therapeut Ltd, Ness Ziona, Israel
[3] Tel Aviv Sourasky Med Ctr, Dept Neurol, Neuroimmunol Lab, Tel Aviv, Israel
[4] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel
关键词
CCR6; CCL20; Experimental autoimmune encephalomyelitis; Multiple sclerosis; Autoantibody; Protective autoimmunity; CENTRAL-NERVOUS-SYSTEM; CHEMOKINE RECEPTOR EXPRESSION; REGULATORY T-CELLS; TH17; CELLS; ENCEPHALOMYELITIS; CCR6; BETA; RECRUITMENT; DISEASE; LESIONS;
D O I
10.1016/j.clim.2017.09.018
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Th-17 type immune response that occurs in multiple sclerosis (MS) is linked to CCR6-CCL20 interaction. We confirmed the dependency on CCR6 in EAE development. Vaccination of mice with hCCL20, but not mCCL20, produced anti-murine CCL20 and ameliorated EAE. The EAE clinical score negatively correlated with anti CCL20 levels. A beneficial effect was transferred by sera from hCCL20-immunized mice. Immunized mice with cyclic peptide that include a bacterial outer membrane protein A (ompA), that share homology sequence with hCCL20 produced anti CCL20, anti ompA and anti-cyclic peptide. Immunization of mice with ompA or the cyclic peptide ameliorated EAE. The cyclic peptide inhibited CCL20 activity in an adhesion assay. A significantly higher level of anti CCL20 were found in healthy individuals compared to RR-MS patients. There was no similar difference for anti-CXCL10. Natural or induced immunization against CCL20 confer protection against EAE and may be beneficial in MS. (C) 2017 Elsevier Inc. All rights reserved.
引用
收藏
页码:316 / 324
页数:9
相关论文
共 46 条
[1]   Astrocytes are the major intracerebral source of macrophage inflammatory protein-3α/CCL20 in relapsing experimental autoimmune encephalomyelitis and in vitro [J].
Ambrosini, E ;
Columba-Cabezas, S ;
Serafini, B ;
Muscella, A ;
Aloisi, F .
GLIA, 2003, 41 (03) :290-300
[2]   CCR5+ and CXCR3+ T cells are increased in multiple sclerosis and their ligands MIP-1α and IP-10 are expressed in demyelinating brain lesions [J].
Balashov, KE ;
Rottman, JB ;
Weiner, HL ;
Hancock, WW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (12) :6873-6878
[3]   The immunology of multiple sclerosis [J].
Bar-Or, Amit .
SEMINARS IN NEUROLOGY, 2008, 28 (01) :29-45
[4]   The CCR5 deletion mutation fails to protect against multiple sclerosis [J].
Bennetts, BH ;
Teutsch, SM ;
Buhler, MM ;
Heard, RNS ;
Stewart, GJ .
HUMAN IMMUNOLOGY, 1997, 58 (01) :52-59
[5]   Phenotypical and functional characterization of T helper 17 cells in multiple sclerosis [J].
Brucklacher-Waldert, Verena ;
Sturner, Klarissa ;
Kolster, Manuela ;
Wolthausen, Julia ;
Tolosa, Eva .
BRAIN, 2009, 132 :3329-3341
[6]   Biomarkers, self-antigens and the immunological homunculus [J].
Cohen, Irun R. .
JOURNAL OF AUTOIMMUNITY, 2007, 29 (04) :246-249
[7]   T-Helper 17 Cells Expand in Multiple Sclerosis and Are Inhibited by Interferon-β [J].
Durelli, Luca ;
Conti, Laura ;
Clerico, Marinella ;
Boselli, Daniela ;
Contessa, Giulia ;
Ripellino, Paolo ;
Ferrero, Bruno ;
Eid, Pierre ;
Novelli, Francesco .
ANNALS OF NEUROLOGY, 2009, 65 (05) :499-509
[8]   Randomised double-blind placebo-controlled study of interferon β-1a in relapsing/remitting multiple sclerosis [J].
Ebers, GC ;
Rice, G ;
Lesaux, J ;
Paty, D ;
Oger, J ;
Li, DKB ;
Beall, S ;
Devonshire, V ;
Hashimoto, S ;
Hooge, J ;
Kastrukoff, L ;
Krieger, C ;
Mezei, M ;
Seland, P ;
Vorobeychi, G ;
Morrison, W ;
Nelson, J ;
Freedman, MS ;
Chrisie, S ;
Nelson, R ;
Rabinovitch, H ;
Freedman, C ;
Hartung, HP ;
Rieckmann, P ;
Archelos, J ;
Jung, S ;
Weilbach, F ;
Flachenecke, P ;
Sauer, J ;
Hommes, O ;
Jongen, P ;
Brouwer, S ;
McLeod, J ;
Pollard, J ;
Ng, R ;
Sandberg-Wollheim, M ;
Källén, K ;
Nilsson, P ;
Ekberg, R ;
Lundgren, A ;
Jadbäck, G ;
Wikström, J ;
Multanen, J ;
Valjakka, M ;
Carton, H ;
Lissoir, F ;
Declerq, I ;
Vieren, M ;
Peeters, E ;
Dubois, B .
LANCET, 1998, 352 (9139) :1498-1504
[9]   Mice deficient for CCR6 fail to control chronic experimental autoimmune encephalomyelitis [J].
Elhofy, Adam ;
DePaolo, R. William ;
Lira, Sergio A. ;
Lukacs, Nicholas W. ;
Karpus, William J. .
JOURNAL OF NEUROIMMUNOLOGY, 2009, 213 (1-2) :91-99
[10]   T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines [J].
Fossiez, F ;
Djossou, O ;
Chomarat, P ;
FloresRomo, L ;
AitYahia, S ;
Maat, C ;
Pin, JJ ;
Garrone, P ;
Garcia, E ;
Saeland, S ;
Blanchard, D ;
Gaillard, C ;
DasMahapatra, B ;
Rouvier, E ;
Golstein, P ;
Banchereau, J ;
Lebecque, S .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (06) :2593-2603