title: Reprogramming of B cells into regulatory cells with engineered fusokines.
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 naive 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.
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
authors.forename: Jiusheng
authors.initials: J
authors.lastname: Deng
authors.forename: Jacques
authors.initials: J
authors.lastname: Galipeau
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy; D015551:Autoimmunity / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D019409:Interleukin-15 / Q000276:immunology; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000276:immunology*
chemical_list: D016207:Cytokines; C518130:GIFT15 protein; D019409:Interleukin-15; D011993:Recombinant Fusion Proteins; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor