Endothelial basement membrane laminin alpha5 selectively inhibits T lymphocyte extravasation into the brain
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Wu, Chuan; Fredrik, Ivars; Anderson, Per Olof; Rupert, Hallmann; Dietmar, Vestweber; Nilsson, Per; Robenek, Horst; Tryggvason, Karl; Song, Jian; Korpos, Eva; Loser, Karin; Beissert, Stefan; Georges-Labouesse, Elisabeth; Sorokin, Lydia MEditorial
Nature
Materia
laminin a5 extravasation brain
Date
2009-05Referencia bibliográfica
Wu, Chuan et al. “Endothelial basement membrane laminin alpha5 selectively inhibits T lymphocyte extravasation into the brain.” Nature medicine vol. 15,5 (2009): 519-27. doi:10.1038/nm.1957
Sponsorship
German Research Council; Swedish Research Council; Alfred O¨sterlunds Foundation; Knut and Alice Wallenbergs Foundation; The Crafoord Foundation; The Greta and Johan Kocks Foundation; The Interdisciplinary Clinical Research CenterAbstract
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 a4 and small amounts of laminin a5. In
mice lacking laminin a4, laminin a5 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 a5 directly inhibited integrin a6b1–mediated migration of T lymphocytes through
laminin a4. 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.