EU researchers unveil how T cell dysfunction triggers MS
French and British scientists have revealed insight into how a critical immune regulatory pathway contributes to the development of multiple sclerosis (MS), potentially paving the way toward future immunotherapies for the debilitating condition.
Though, it’s clear that a T cell dysfunction drives the autoimmune disease, mystery still surrounds the mechanisms that cause the immune systems of people with MS to attack the protective myelin sheath surrounding neurons in the brain and spinal cord. No cures exist, but scientists have determined that MS and other chronic autoimmune conditions like asthma share one key immune defect – so-called T helper cells (TH1) fail to develop normally into type 1 regulatory T cells (Tr1), which tamp down inflammation and prevent overactivation of T killer cells which often results in inappropriate reactions against a person’s own tissues.
Lead author Siobhan Ni Choileain and colleagues from INSERM in Toulouse uncovered a glitch in T cells from MS patients that altered the processing of a crucial regulatory protein called CD46, which controls the transition from TH1 to Tr1. In healthy cells, activation by the T cell receptor led to alterations in how CD46 was modified by glycosylation – a change that did not occur in cells isolated from MS patients. The authors say their findings suggest a possible mechanism underlying the regulatory function of CD46 on T cells.