A new study entitled “Intestinal Barrier Dysfunction Develops at the Onset of Experimental Autoimmune Encephalomyelitis, and Can Be Induced by Adoptive Transfer of Auto-Reactive T Cells” published in September issue of PloS One, reports that disruption of intestinal homeostasis supports Experimental Autoimmune Encephalomyelitis, the prototypic mouse model of human Multiple sclerosis.
Multiple sclerosis (MS) is an inflammatory autoimmune disorder characterized by targeted destruction of myelin — a major component of the central nervous system — by self-reactive inflammatory T cells. Recent observations suggest an association between MS and inflammatory bowel disease (IBD), with increased incidence of Crohn’s disease (CD) and ulcerative colitis (UC), the two most common types of IBD, among MS patients. IBD is characterized by a chronic inflammation of the gastrointestinal tract, leading to disruption of the intestinal epithelial barrier, a phenomenon known as “leaky gut.” This loss of epithelial barrier function may allow luminal antigens to abnormally activate the host-immune response leading to a systemic autoimmune response. In the present study, the authors evaluated if Experimental Autoimmune Encephalomyelitis (EAE), a model for human MS in rodents, is accompanied by loss of mucosal immune homeostasis.
The authors induced EAE in rodents and studied the intestinal tissue of these mice. They found significant structural alterations in the intestinal epithelia morphology of EAE mice together with increasing levels of infiltrated inflammatory T-cells. On the contrary, regulatory T cells’ levels were impaired in EAE-mice – a specific subpopulation of T cells that suppress the immune response, therefore, preventing immune system excessive response. These changes were observed even before the onset of neurological symptoms (until day 7) and were maintained at the paralysis stage (14 days after EAE induction). The researchers performed further studies and isolated EAE T cells from diseased mice, and transferred it to healthy mice. The transfer led to the same intestinal alterations as seen in EAE-induced mice.
The team of researchers at the Department of Biology, Lund University, Lund, Sweden suggests the loss of intestinal homeostasis may support EAE progression by inducing a systemic and chronic inflammatory state.
The authors propose that further studies that allow researchers to understand the molecular pathways needed to restore intestinal barrier homeostasis will provide innovative therapeutics to MS patients.