An albumin interleukin 33 fusion protein with enhanced lymph node retention suppresses murine models of multiple sclerosis

Abstract Interleukin-33 (IL-33) is an immunoregulatory cytokine that suppresses pathogenic Th17 T cells. Recombinant IL-33 has been shown to prevent disease onset in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. However, the systemic administration not clinically translated, part because cytokine’s short half-life makes it difficult achieve therapeutically effective concentrations secondary lymphoid organs. To overcome this challenge, we have recombinantly fused mouse serum albumin (SA) IL-33. ST2(IL-33R)-expressing group 2 innate cells treated with (SA IL-33) increased CD25 expression and IL-13 production dose-dependent manner. SA fusion prolonged its concentration lymph nodes naïve C57BL/6 mice. Prophylactic prevented MOG-induced EAE, demonstrating equal efficacy approved MS drug fingolimod. In mice already-established reduced score improved weight gain. At cellular level, SA-IL-33 treatment frequency CD45+ cells, including causing Rorgt+ CD4+ spinal cord. EAE displayed increase ST2+ FoxP3+ CD25+ Tregs Th2 both spleen cord draining nodes, suggesting by expanding protective type response.