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Published on: February 23, 2024
Soluble CD40 ligand disrupts the blood-brain barrier and exacerbates inflammation in experimental autoimmune
Hiroki Masuda1, Masahiro Mori1, Kenta Umehara2
1Department of Neurology, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8670, Japan.
Abstract:
Serum soluble CD40 ligand (sCD40L) has been reported to positively correlate with the albumin quotient, a marker of blood-brain barrier (BBB) breakdown, in patients with multiple sclerosis (MS). To clarify the mechanisms of sCD40L in MS pathophysiology, sCD40L was administered to experimental autoimmune encephalomyelitis (EAE) mice and a human brain microvascular endothelial cell (HBMEC)-based BBB model. The high-dose sCD40L group showed a worse EAE score than the low-dose and control groups. BBB permeability was increased by administering sCD40L in a HBMEC-based BBB model. Thus, sCD40L induces more severe inflammation in the central nervous system by disrupting the BBB.
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