Title:Reprogramming of B Cells into Regulatory Cells with Engineered Fusokines
Volume: 12
Issue: 3
Author(s): Jiusheng Deng and Jacques Galipeau
Affiliation:
Keywords:
Fusokine, GM-CSF, IL-10; IL-15, bregs, inflammation, multiple sclerosis, pathogenic microorganisms, autoimmune diseases, anti-inflammatory cytokine, autoimmune ailments, immune response, fusokines, potent therapeutic tool, pathogenic microorganismal
Abstract: B cells play a pivotal role in host adaptive immunity against pathogenic microorganisms, but may also maladaptively
contribute to the pathogenesis of autoimmune diseases. In contrast, distinct B cell subsets have the capacity to
regulate host immune response, and suppress inflammation. B regulatory cells are a rare population of endogenous Blymphocytes
defined in part by production of the anti-inflammatory cytokine IL-10. Although “natural” B regulatory cells
exist in vivo, the low frequency of B regulatory cells may be a limiting factor on their impact in autoimmune ailments. In
answer to this unmet need, we have developed a novel strategy for alternate lymphoid activation: fusokines. These wholly
engineered chimeric leukines fuse two functionally unrelated cytokines for the purpose of alternate immune modulation.
The GM-CSF- and IL-15-derived fusokine: GIFT15, possesses entirely novel and unheralded immune modulating properties
mediated through the IL15 receptor which reprograms naïve B cells into B regulatory cells (Bregs). In this article, we
review the current approaches to generate Bregs in vitro, and highlight gain-of-function mechanisms by which GIFT15-
induced Bregs abrogate pathogenic autoimmunity in mice. We also demonstrate that the human equivalent of inducible
Bregs may also serve as a new potent therapeutic tool for treatment of autoimmune disease.
