Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation

被引:1302
作者
Kebir, Hania
Kreymborg, Katharina
Ifergan, Igal
Dodelet-Devillers, Aurore
Cayrol, Romain
Bernard, Monique
Giuliani, Fabrizio
Arbour, Nathalie
Becher, Burkhard
Prat, Alexandre
机构
[1] Univ Montreal, Notre Dame Hosp, Ctr Hosp, Ctr Study Brain Dis,Neuroimmunol Unit, Montreal, PQ H2L 4M1, Canada
[2] Univ Zurich, Dept Neurol, Div Neuroimmunol, CH-8057 Zurich, Switzerland
[3] Univ Alberta, Dept Med, Div Neurol, Edmonton, AB T6G 2G3, Canada
基金
加拿大健康研究院;
关键词
D O I
10.1038/nm1651
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
T(H)17 lymphocytes appear to be essential in the pathogenesis of numerous inflammatory diseases. We demonstrate here the expression of IL- 17 and IL- 22 receptors on blood- brain barrier endothelial cells (BBB-ECs) in multiple sclerosis lesions, and show that IL- 17 and IL- 22 disrupt BBB tight junctions in vitro and in vivo. Furthermore, T(H)17 lymphocytes transmigrate efficiently across BBB-ECs, highly express granzyme B, kill human neurons and promote central nervous system inflammation through CD4(+) lymphocyte recruitment.
引用
收藏
页码:1173 / 1175
页数:3
相关论文
共 14 条
  • [1] Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis
    Bettelli, E
    Sullivan, B
    Szabo, SJ
    Sobel, RA
    Glimcher, H
    Kuchroo, VK
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (01) : 79 - 87
  • [2] Regulation of Th1 and Th2 lymphocyte migration by human adult brain endothelial cells
    Biernacki, K
    Prat, A
    Blain, M
    Antel, JP
    [J]. JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2001, 60 (12) : 1127 - 1136
  • [3] Expression and regulation of IL-22 in the IL-17-producing CD4+T lymphocytes
    Chung, Yeonseok
    Yang, Xuexian
    Chang, Seon Hee
    Ma, Li
    Tian, Qiang
    Dong, Chen
    [J]. CELL RESEARCH, 2006, 16 (11) : 902 - 907
  • [4] Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain
    Cua, DJ
    Sherlock, J
    Chen, Y
    Murphy, CA
    Joyce, B
    Seymour, B
    Lucian, L
    To, W
    Kwan, S
    Churakova, T
    Zurawski, S
    Wiekowski, M
    Lira, SA
    Gorman, D
    Kastelein, RA
    Sedgwick, JD
    [J]. NATURE, 2003, 421 (6924) : 744 - 748
  • [5] IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis
    Komiyama, Yutaka
    Nakae, Susumu
    Matsuki, Taizo
    Nambu, Aya
    Ishigame, Harumichi
    Kakuta, Shigeru
    Sudo, Katsuko
    Iwakura, Yoichiro
    [J]. JOURNAL OF IMMUNOLOGY, 2006, 177 (01) : 566 - 573
  • [6] IL-23 drives a pathogenic T cell population that induces autoimmune inflammation
    Langrish, CL
    Chen, Y
    Blumenschein, WM
    Mattson, J
    Basham, B
    Sedgwick, JD
    McClanahan, T
    Kastelein, RA
    Cua, DJ
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (02) : 233 - 240
  • [7] Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides
    Liang, Spencer C.
    Tan, Xiang-Yang
    Luxenberg, Deborah P.
    Karim, Riyez
    Dunussi-Joannopoulos, Kyriaki
    Collins, Mary
    Fouser, Lynette A.
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (10) : 2271 - 2279
  • [8] Th1 and Th2 lymphocyte migration across the human BBB is specifically regulated by interferon β and copolymer-1
    Prat, A
    Biernacki, K
    Antel, JP
    [J]. JOURNAL OF AUTOIMMUNITY, 2005, 24 (02) : 119 - 124
  • [9] SELECTIVE ENRICHMENT OF T(H)1 CD45RB(LOW) CD4+ T-CELLS IN AUTOIMMUNE INFILTRATES IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS
    RENNO, T
    ZEINE, R
    GIRARD, JM
    GILLANI, S
    DODELET, V
    OWENS, T
    [J]. INTERNATIONAL IMMUNOLOGY, 1994, 6 (03) : 347 - 354
  • [10] Immunology of multiple sclerosis
    Sospedra, M
    Martin, R
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 2005, 23 : 683 - 747