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CD99L2 deficiency inhibits leukocyte entry into the central nervous system and ameliorates neuroinflammation
Author(s) -
Samus Maryna,
Seelige Ruth,
Schäfer Kerstin,
Sorokin Lydia,
Vestweber Dietmar
Publication year - 2018
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.1a0617-228r
Subject(s) - experimental autoimmune encephalomyelitis , blood–brain barrier , neuroinflammation , biology , central nervous system , endothelium , immunology , multiple sclerosis , immune system , cell adhesion molecule , basement membrane , microbiology and biotechnology , inflammation , neuroscience , endocrinology
Leukocyte entry into the CNS is a crucial step in the development of multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). Adhesion molecules mediating the docking of leukocytes to the endothelium of the blood–brain barrier (BBB) represent valuable targets for interference with the disease. However, little is known about the adhesion and signaling mechanisms in endothelial cells that mediate the diapedesis through the BBB. Here, we show that conditional Tie‐2‐Cre driven gene inactivation of CD99L2 inhibits leukocyte entry into the CNS during active MOG 35‐55 ‐induced EAE and alleviates severity of the disease. No detrimental effect on the immune response was observed. The number of perivascular cuffs around vessels of the CNS was reduced, as was the number of inflammatory foci, sites of demyelination and expression levels of pro‐inflammatory cytokines. Three‐dimensional analysis of vibratome sections of the CNS revealed an accumulation of leukocytes between endothelial cells and the underlying basement membrane, whereas leukocyte docking to the luminal surface of the endothelium of the BBB was unaffected. Collectively, these results suggest that CD99L2 participates in the development of EAE by supporting diapedesis of leukocytes through the endothelial basement membrane of blood vessels of the BBB in the CNS.