A unique population of B cells may play a role in the future treatment of autoimmune uveitis, according to a recent study by researchers from the National Eye Institute (NEI). In their study, infusions of purified IL-27 regulatory B cells (I27-Breg) were found to successfully reduce symptoms of autoimmune uveitis and multiple sclerosis in mice.
Uveitis is a group of sight-threatening inflammatory eye diseases that includes Behcet disease, birdshot retinochoroidopathy, and sympathetic ophthalmia. It is characterized by repeated cycles of intraocular inflammation. While corticosteroids can be used to treat the disease, prolonged use of these drugs risks other eye problems such as optic neuropathy and steroid-induced glaucoma.
“We are the first to describe this unique population of regulatory B cells. While similar in function to other Bregs, I27-Breg have a distinct gene expression profile and originate from the innate B-1a cell lineage,” said Charles Egwuagu, Ph.D., M.P.H., who directs the NEI Molecular Immunology Section. He and colleagues published their findings in PNAS.
Egwuagu and colleagues used a variety of assays to demonstrate the existence of IL-27-producing regulatory B cells (i27-Bregs) in the peritoneal cavity of mice. Further analyses showed that upon encounter with innate immune stimuli, the cells, which come from B-1a lineage B cells, lose their ability to produce natural IgM antibodies and differentiate into IL-27-producing B-1a cells. They then migrate from the peritoneal cavity to secondary lymphoid tissues such as the spleen. The researchers also found significant amounts of i27-Bregs in human umbilical cord blood.
The researchers next examined whether i27-Breg immunotherapy would be effective in suppressing autoimmune uveitis or a multiple sclerosis (MS)-like disease in mice. Infusion of purified i27-Breg ameliorated uveitis and MS through up-regulation of inhibitory receptors (Lag3, PD-1), suppression of T-cell (Th17/Th1) responses, and propagation of inhibitory signals that converted conventional B cells to regulatory lymphocytes that secrete IL-10 and/or IL-35 in eye, brain, and spinal cord. Additionally, they found that i27-Bregs proliferate in vivo and sustain IL-27 secretion in CNS and lymphoid tissues, a therapeutic advantage over administering IL-10 or IL-35 biologics, which are rapidly cleared in the body. i27-Breg infusions into mice lacking the IL-27 receptor failed to attenuate disease symptoms, demonstrating that IL-27 is necessary for successful treatment. i27-Bregs are neither antigen-specific nor disease-specific, suggesting that they would be effective immunotherapy for a wide spectrum of autoimmune diseases.
Full news release: www.nei.nih.gov/about/news-and-events/news/nih-scientists-discover-new-b-cell-tempers-autoimmunity
Source: National Eye Institute