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1.	Wu, Chuan, et al. (författare) Endothelial basement membrane laminin alpha 5 selectively inhibits T lymphocyte extravasation into the brain 2009 Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 15:5, s. 519-527 Tidskriftsartikel (refereegranskat)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.

Wu, Chuan, et al. (författare)
Endothelial basement membrane laminin alpha 5 selectively inhibits T lymphocyte extravasation into the brain
2009
Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 15:5, s. 519-527
Tidskriftsartikel (refereegranskat)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.

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