A study conducted by researchers at The University of Texas MD Anderson Cancer Center identified a protein regulator called Trabid as a key player on the complex chain of events that lead to autoimmune inflammation of the central nervous system (CNS) in patients with multiple sclerosis (MS).
The study, “Epigenetic regulation of the expression of Il12 and Il23 and autoimmune inflammation by the deubiquitinase Trabid,” was published in the online issue of Nature Immunology.
Dr. Shao-Cong Sun, professor of immunology and the study’s senior author, and his team found that the removal of a protein-coding gene named Zranb1 – which encodes Trabid – in dendritic cells inhibited the expression of interleukin (IL)-12 and IL-23, inhibiting differentiation of inflammatory immune T-cells.
Both IL-12 and IL-23 are mediators of inflammation and associated with inflammatory diseases.
“Cells of the innate immune system, including dendritic cells and macrophages, have an important role in regulating the nature and magnitude of adaptive immune responses,” Sun said in a press release. “They recognize microbial components including various receptors that trigger intracellular signaling events that impact the function of those cells. Deregulated production of pro-inflammatory cytokines by cells of the innate immune system also contributes to autoimmune and inflammatory diseases.”
IL-12 and IL-23 are pro-inflammatory cytokines that connect innate responses and immune responses, according to the study’s authors. The innate immune system — the nonspecific immune system — is a critical subcategory of the overall immune system, and includes mechanisms and cells that shield the host against infection by foreign bodies.
“Our findings highlight an epigenetic mechanism for the regulation of the cytokine genes, IL-12 and IL-23, and established Trabid as an immunological regulator of inflammatory T-cell responses,” Sun said. “Trabid appeared to regulate histone modifications by controlling the fate of a histone demethylase called Jmjd2d.”
Sun believes that Trabid and Jmjd2d may be potential therapeutic targets for the treatment of inflammatory diseases, such as MS and cancer. “Since chronic inflammation is a major risk of cancer, future studies will examine whether Trabid and Jmjd2d also have a role in cancer development,” he said.
MS is a devastating inflammatory disease estimated to affect 2.3 million people worldwide. Inflammation is an important part of the body’s response against infections and tissue damage, but unresolved inflammation contributes to the pathogenesis of a variety of diseases and promotes cancer development.
MS and other inflammatory diseases may benefit from new findings identifying potential therapeutic targets such as Trabid.