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

Summary, in English

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: Chuan Wu; Fredrik Ivars; Per Anderson; Rupert Hallmann; Dietmar Vestweber; Per Nilsson; Horst Robenek; Karl Tryggvason; Jian Song; Eva Korpos; Karin Loser; Stefan Beissert; Elisabeth Georges-Labouesse; Lydia M. Sorokin
• Department/s: Immunology
• Publishing year: 2009
• Language: English
• Pages: 519-527
• Publication/Series: Nature Medicine
• Volume: 15
• Issue: 5
• Links: http://dx.doi.org/10.1038/nm.1957
• Document type: Journal article
• Publisher: Nature Publishing Group
• Topic: Immunology in the medical area
• Status: Published
• Research group: Immunology
• ISBN/ISSN/Other: ISSN: 1546-170X