Cutting Edge: Loss of α4 Integrin Expression Differentially Affects the Homing of Th1 and Th17 Cells

被引:66
作者
Glatigny, Simon [1 ]
Duhen, Rebekka [1 ]
Oukka, Mohamed [2 ,3 ]
Bettelli, Estelle [1 ,3 ]
机构
[1] Benaroya Res Inst, Program Immunol, Seattle, WA 98101 USA
[2] Seattle Childrens Hosp Res Fdn, Ctr Immun & Immunotherapies, Div Immunol, Seattle, WA 98101 USA
[3] Univ Washington, Dept Immunol, Seattle, WA 98105 USA
基金
美国国家卫生研究院;
关键词
EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS; T-CELLS; RESPONSES; ALPHA-4-BETA-7-INTEGRIN; NATALIZUMAB; T(H)17; VLA-4;
D O I
10.4049/jimmunol.1102515
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The neutralization of alpha 4 integrin is currently used as treatment in several autoimmune diseases and is thought to prevent the entry of most immune cells in target tissues. In this study, we showed that selective deletion of alpha 4 integrin in T cells did not prevent but delayed the development of experimental autoimmune encephalomyelitis. Whereas both Th1 and Th17 cells infiltrate the CNS of wild-type mice, T cells present in the CNS of mice lacking alpha 4 integrin were mainly enriched in Th17 cells, suggesting that this T cell subset uses other integrins to access the CNS. In contrast, alpha 4 integrin expression is important for Th1 cells to enter the CNS and for the stability of their Th1-associated genetic program. Therefore, our data suggest that anti-alpha 4 integrin Ab treatment may be more efficient in the treatment of Th1-rather than Th17-mediated disease. The Journal of Immunology, 2011, 187: 6176-6179.
引用
收藏
页码:6176 / 6179
页数:4
相关论文
共 19 条
[1]   T helper type 1 and 17 cells determine efficacy of interferon-β in multiple sclerosis and experimental encephalomyelitis [J].
Axtell, Robert C. ;
de Jong, Brigit A. ;
Boniface, Katia ;
van der Voort, Laura F. ;
Bhat, Roopa ;
De Sarno, Patrizia ;
Naves, Rodrigo ;
Han, May ;
Zhong, Franklin ;
Castellanos, Jim G. ;
Mair, Robert ;
Christakos, Athena ;
Kolkowitz, Ilan ;
Katz, Liat ;
Killestein, Joep ;
Polman, Chris H. ;
Malefyt, Rene de Waal ;
Steinman, Lawrence ;
Raman, Chander .
NATURE MEDICINE, 2010, 16 (04) :406-U21
[2]   Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells [J].
Bettelli, E ;
Carrier, YJ ;
Gao, WD ;
Korn, T ;
Strom, TB ;
Oukka, M ;
Weiner, HL ;
Kuchroo, VK .
NATURE, 2006, 441 (7090) :235-238
[3]   Induction and effector functions of TH17 cells [J].
Bettelli, Estelle ;
Korn, Thomas ;
Oukka, Mohamed ;
Kuchroo, Vijay K. .
NATURE, 2008, 453 (7198) :1051-1057
[4]   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
[5]   TET inducible expression of the α4β7-integrin ligand MAdCAM-1 on the blood-brain barrier does not influence the immunopathogenesis of experimental autoimmune encephalomyelitis [J].
Doering, Axinia ;
Pfeiffer, Friederike ;
Meier, Matthias ;
Dehouck, Benedicte ;
Tauber, Silke ;
Deutsch, Urban ;
Engelhardt, Britta .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2011, 41 (03) :813-821
[6]   The development of experimental autoimmune encephalomyelitis in the mouse requires α4-integrin but not α4β7-integrin [J].
Engelhardt, B ;
Laschinger, M ;
Schulz, M ;
Samulowitz, U ;
Vestweber, D ;
Hoch, G .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (12) :2096-2105
[7]   T cells in multiple sclerosis and experimental autoimmune encephalomyelitis [J].
Fletcher, J. M. ;
Lalor, S. J. ;
Sweeney, C. M. ;
Tubridy, N. ;
Mills, K. H. G. .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2010, 162 (01) :1-11
[8]   Fate mapping of IL-17-producing T cells in inflammatory responses [J].
Hirota, Keiji ;
Duarte, Joao H. ;
Veldhoen, Marc ;
Hornsby, Eve ;
Li, Ying ;
Cua, Daniel J. ;
Ahlfors, Helena ;
Wilhelm, Christoph ;
Tolaini, Mauro ;
Menzel, Ursula ;
Garefalaki, Anna ;
Potocnik, Alexandre J. ;
Stockinger, Brigitta .
NATURE IMMUNOLOGY, 2011, 12 (03) :255-U95
[9]   Integrins: Bidirectional, allosteric signaling machines [J].
Hynes, RO .
CELL, 2002, 110 (06) :673-687
[10]   Reevaluation of P-selectin and α4 integrin as targets for the treatment of experimental autoimmune encephalomyelitis [J].
Kerfoot, Steven M. ;
Norman, M. Ursula ;
Lapointe, Benoit M. ;
Bonder, Claudine S. ;
Zbytnuik, Lori ;
Kubes, Paul .
JOURNAL OF IMMUNOLOGY, 2006, 176 (10) :6225-6234