An inflammation amplification loop in endothelial cells regulated by cytokines and neural activation — ASN Events

An inflammation amplification loop in endothelial cells regulated by cytokines and neural activation (#S-36)

Masaaki Murakami

The central nervous system (CNS) is an immune-privileged region protected by the brain-blood barrier (BBB). Upon infection or traumatic injury in the CNS, the BBB is breached, and various immune cells are recruited to the affected area. In autoimmune diseases like multiple sclerosis (MS), autoreactive T cells can attack self-neurons throughout the CNS. This phenomenon raises the possibility that there exists specific signals that direct autoreactive T cells past the BBB and into particular sites of the CNS. Using a MS mouse model, experimental autoimmune encephalomyelitis (EAE), we defined the mechanism for a pathogenesis in which regional neural stimulations modulate the status of the blood vessel endothelium to allow the invasion of autoreactive T cells into specific sites of the CNS via the fifth lumbar cord. This gate for autoreactive T cells can be artificially manipulated by removing gravity force on the hind legs or by electric pulses to the soleus muscles, quadriceps, or triceps of mice, resulting in an accumulation of autoreactive T cells in the intended regions via the activation of regional neurons. Gating blood vessels by local neural stimulations, a phenomenon we call the gateway reflex, has potential therapeutic value not only in preventing autoimmunity, but also in augmenting the effects of cancer immunotherapies via artificial neural stimulations.