A recent study published in Nature Communications showed, for the first time, that a protein complex called LUBAC is responsible for controlling the late-stage development of immune T-cells before they are released into the bloodstream.
Several types of cells compose the immune system, working together to fight infections or cancer. Among these are T-cells, which need to pass through the thymus, where bad cells are eliminated and others are taught to fight disease. Only a small number of T-cells pass this developmental process and are allowed out of the thymus.
The study, “Linear ubiquitin chain assembly complex coordinates late thymic T-cell differentiation and regulatory T-cell homeostasis,” led by Dr. Charis Teh, Dr. Daniel Gray and colleagues, found that faulty LUBAC activity caused defective T-cell development, with major impacts on autoimmune response.
“By showing that LUBAC is essential for T-cell development, we also revealed a new stage of ‘T-cell education’ that had not previously been appreciated. We’re excited by the prospect that this new checkpoint may be important for ensuring autoimmune T-cells are not allowed to complete their development,” Teh said in a press release.
The new findings can have major implications on the understanding of multiple sclerosis (MS), Teh said. “In most people, this prevents the development of autoimmune diseases such as type 1 diabetes and multiple sclerosis.”
MS is an autoimmune disease characterized by uncontrolled autoreactive T-cells. So far this was thought to be due to the inability of a subset of T-cells called regulatory T-cells to suppress the defective immune cells in MS patients. These new findings further explain and support what is known.
Increased understanding of the processes implicated in the regulation of the immune system and its response may lead to the development of new approaches to “switch off” autoimmune T-cells. “This may have therapeutic applications in the future for treating autoimmune diseases,” Gray said.
“Another interesting aspect of this research relates to rare inherited immune disorders caused by defects in the genes that encode the components of LUBAC,” Gray added. “Our research has provided new insights into how these disorders are linked to faulty T-cell function. This may inspire new immune-based therapies for these conditions.”