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Endothelial basement membrane laminin alpha 5 selectively inhibits T lymphocyte extravasation into the brain

Wu, Chuan; Ivars, Fredrik LU ; Anderson, Per LU ; Hallmann, Rupert; Vestweber, Dietmar; Nilsson, Per; Robenek, Horst; Tryggvason, Karl; Song, Jian and Korpos, Eva, et al. (2009) In Nature Medicine 15(5). p.519-527
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 alpha 4 and small amounts of laminin alpha 5. In mice lacking laminin alpha 4, laminin alpha 5 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... (More)
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 alpha 4 and small amounts of laminin alpha 5. In mice lacking laminin alpha 4, laminin alpha 5 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 alpha 5 directly inhibited integrin alpha(6)beta(1)-mediated migration of T lymphocytes through laminin alpha 4. 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. (Less)
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publication status
published
subject
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Nature Medicine
volume
15
issue
5
pages
519 - 527
publisher
Nature Publishing Group
external identifiers
  • wos:000265889300030
  • scopus:67349162632
ISSN
1546-170X
DOI
10.1038/nm.1957
language
English
LU publication?
yes
id
4f70fea4-55e2-4713-8b0c-c2471d8d691d (old id 1425865)
date added to LUP
2009-06-26 15:03:32
date last changed
2017-12-10 04:04:53
@article{4f70fea4-55e2-4713-8b0c-c2471d8d691d,
  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 alpha 4 and small amounts of laminin alpha 5. In mice lacking laminin alpha 4, laminin alpha 5 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 alpha 5 directly inhibited integrin alpha(6)beta(1)-mediated migration of T lymphocytes through laminin alpha 4. 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.},
  author       = {Wu, Chuan and Ivars, Fredrik and Anderson, Per and Hallmann, Rupert and Vestweber, Dietmar and Nilsson, Per and Robenek, Horst and Tryggvason, Karl and Song, Jian and Korpos, Eva and Loser, Karin and Beissert, Stefan and Georges-Labouesse, Elisabeth and Sorokin, Lydia M.},
  issn         = {1546-170X},
  language     = {eng},
  number       = {5},
  pages        = {519--527},
  publisher    = {Nature Publishing Group},
  series       = {Nature Medicine},
  title        = {Endothelial basement membrane laminin alpha 5 selectively inhibits T lymphocyte extravasation into the brain},
  url          = {http://dx.doi.org/10.1038/nm.1957},
  volume       = {15},
  year         = {2009},
}