Data presented at the European Committee for Treatment and Research in Multiple Sclerosis Congress in Barcelona suggest a potential role of the dual immunoglobulin domain containing cell adhesion molecule (DICAM) in the transmigration and recruitment of TH17 across central nervous system (CNS) vascular barriers. Previous research indicated that DICAM is up-regulated in TH17 lymphocytes.
In the present study, Soufiane Ghannam, PhD, of the Montreal University Health Center in Montreal, and colleagues aimed to better understand the expression and function of DICAM in autoimmune neuroinflammation, assessing the role of DICAM in CNS inflammation and the migration of encephalitogenic TH17 lymphocytes to the CNS.
Utilizing blood from healthy donors and patients with multiple sclerosis (MS), Ghannam and colleagues used quantitative polymerase chain reaction (qPCR) and flow cytometry of differentiated TH1, TH2, and TH17 lymphocytes and a different subset of human immune cells to determine DICAM expression. A large collection of CNS material culled from experimental autoimmune encephalomyelitis animals, MS patients, and controls was used to gauge DICAM expression.
Results indicate that TH17 lymphocytes primarily expressed DICAM. Furthermore, the expression of DICAM was strongly linked with expression of ROR-γ, IL-23R, IL-17, IL-22, GM-CSF, and GZMB expression in human CD4+ lymphocytes, as well as to a lesser extent in TH1 CD4+ lymphocytes.
“These data are the first to demonstrate that DICAM is specifically expressed on the surface of potentially encephalitogenic TH17 lymphocytes, and that expression of DICAM is regulated by IL-23, IL-1 and IL-6 — cytokines which are involved in CNS autoimmune diseases,” Dr. Ghannam and colleagues wrote.
In confocal microscopy analysis of MS brain lesions, DICAM-expressing CD4+ T lymphocytes were present in active demyelinating lesions and in some early pre-active lesions. DICAM-expressing cells also co-expressed IL-17.
Additionally, in qPCR analysis of DICAM expression in CD4+ and CD8+T lymphocytes, which was collected from the blood of MS patients, there was a significant DICAM up-regulation in untreated relapsing-remitting MS patients vs. healthy donors.
“These data are in strong support of the role that DICAM could play in the transmigration and the recruitment of TH17 lymphocytes across CNS vascular barriers,” Dr. Ghannam and colleagues concluded.
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- Ghannam S et al. Abstract 132. Presented at: The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress; Oct. 7-10, 2015; Barcelona.