Endothelial basement membrane laminin alpha5 selectively inhibits T lymphocyte extravasation into the brain.

Chuan Wu 1 Fredrik Ivars 2 Per Anderson 2 Rupert Hallmann 1 Dietmar Vestweber 3 Per Nilsson 4 Horst Robenek 5 Karl Tryggvason 6 Jian Song 1 Eva Korpos 1 Karin Loser 7 Stefan Beissert 7 Elisabeth Georges-Labouesse 8 Lydia Sorokin 1
1 Institute for Physiological Chemistry and Pathobiochemistry
2 Section for Immunology, Department of Experimental Medical Science
3 Vascular Cell Biology
4 Radiation Physics
5 Leibniz Institute for Arterosclerosis Research
6 Department of Medical Biochemistry and Biophysics
7 Department of Dermatology
8 IGBMC - Institut de génétique et biologie moléculaire et cellulaire
Abstract : Specific inhibition of the entry of encephalitogenic T lymphocytes into the central nervous system in multiple sclerosis would provide a means of inhibiting disease without compromising innate immune responses. We show here that targeting lymphocyte interactions with endothelial basement membrane laminins provides such a possibility. In mouse experimental autoimmune encephalomyelitis, T lymphocyte extravasation correlates with sites expressing laminin alpha4 and small amounts of laminin alpha5. In mice lacking laminin alpha4, laminin alpha5 is ubiquitously expressed along the vascular tree, resulting in marked and selective reduction of T lymphocyte infiltration into the brain and reduced disease susceptibility and severity. Vessel phenotype and immune response were not affected in these mice. Rather, laminin alpha5 directly inhibited integrin alpha(6)beta(1)-mediated migration of T lymphocytes through laminin alpha4. The data indicate that T lymphocytes use mechanisms distinct from other immune cells to penetrate the endothelial basement membrane barrier, permitting specific targeting of this immune cell population.
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Nature Medicine, Nature Publishing Group, 2009, 15 (5), pp.519-27. 〈10.1038/nm.1957〉
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http://www.hal.inserm.fr/inserm-00420073
Contributeur : Maité Peney <>
Soumis le : lundi 28 septembre 2009 - 10:14:34
Dernière modification le : jeudi 11 janvier 2018 - 06:17:42

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Chuan Wu, Fredrik Ivars, Per Anderson, Rupert Hallmann, Dietmar Vestweber, et al.. Endothelial basement membrane laminin alpha5 selectively inhibits T lymphocyte extravasation into the brain.. Nature Medicine, Nature Publishing Group, 2009, 15 (5), pp.519-27. 〈10.1038/nm.1957〉. 〈inserm-00420073〉

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