Reprogramming of B Cells into Regulatory Cells with Engineered Fusokines

Author(s): Jiusheng Deng, Jacques Galipeau.

Journal Name: Infectious Disorders - Drug Targets

Volume 12 , Issue 3 , 2012

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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.

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,

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Article Details

VOLUME: 12
ISSUE: 3
Year: 2012
Page: [248 - 254]
Pages: 7
DOI: 10.2174/187152612800564392
Price: $58

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