EGFL7 reduces CNS inflammation in mouse

Catherine Larochelle, Timo Uphaus, Bieke Broux, Elizabeth Gowing, Magdalena Paterka, Laure Michel, Nevenka Dudvarski Stankovic, Frank Bicker, Florent Lemaître, Alexandre Prat, Mirko H. H. Schmidt and Frauke Zipp ()
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Catherine Larochelle: University Medical Center of the Johannes Gutenberg University Mainz
Timo Uphaus: University Medical Center of the Johannes Gutenberg University Mainz
Bieke Broux: Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM)
Elizabeth Gowing: Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM)
Magdalena Paterka: University Medical Center of the Johannes Gutenberg University Mainz
Laure Michel: Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM)
Nevenka Dudvarski Stankovic: University Medical Center of the Johannes Gutenberg University Mainz
Frank Bicker: University Medical Center of the Johannes Gutenberg University Mainz
Florent Lemaître: Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM)
Alexandre Prat: Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM)
Mirko H. H. Schmidt: University Medical Center of the Johannes Gutenberg University Mainz
Frauke Zipp: University Medical Center of the Johannes Gutenberg University Mainz

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Extracellular matrix (ECM) proteins secreted by blood-brain barrier (BBB) endothelial cells (ECs) are implicated in cell trafficking. We discovered that the expression of ECM epidermal growth factor-like protein 7 (EGFL7) is increased in the CNS vasculature of patients with multiple sclerosis (MS), and in mice with experimental autoimmune encephalomyelitis (EAE). Perivascular CD4 T lymphocytes colocalize with ECM-bound EGFL7 in MS lesions. Human and mouse activated T cells upregulate EGFL7 ligand αvβ3 integrin and can adhere to EGFL7 through integrin αvβ3. EGFL7-knockout (KO) mice show earlier onset of EAE and increased brain and spinal cord parenchymal infiltration of T lymphocytes. Importantly, EC-restricted EGFL7-KO is associated with a similar EAE worsening. Finally, treatment with recombinant EGFL7 improves EAE, reduces MCAM expression, and tightens the BBB in mouse. Our data demonstrate that EGFL7 can limit CNS immune infiltration and may represent a novel therapeutic avenue in MS.

Date: 2018
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DOI: 10.1038/s41467-018-03186-z

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