Journal
NATURE MEDICINE
Volume 15, Issue 5, Pages 519-527Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.1957
Keywords
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Funding
- German [SFB293 A14, B8, A1, SFB492 Z3]
- Swedish Research Councils [K2005-06X-14184-04A, 621-2001-2142]
- Alfred Osterlunds Foundation
- Knut and Alice Wallenbergs Foundation [KAW 2002.0056]
- Crafoord Foundation
- Greta
- Johan Kocks Foundation
- Interdisciplinary Clinical Research Center [Lo2/017/07]
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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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