title: Milk-based nutraceutical for treating autoimmune arthritis via the stimulation of IL-10- and TGF-β-producing CD39+ regulatory T cells.
abstract: Autoimmune diseases arise from the loss of tolerance to self, and because the etiologies of such diseases are largely unknown, symptomatic treatments rely on anti-inflammatory and analgesic agents. Tolerogenic treatments that can reverse disease are preferred, but again, often thwarted by not knowing the responsible auto-antigens (auto-Ags). Hence, a viable alternative to stimulating regulatory T cells (Tregs) is to induce bystander tolerance. Colonization factor antigen I (CFA/I) has been shown to evoke bystander immunity and to hasten Ag-specific Treg development independent of auto-Ag. To translate in treating human autoimmune diseases, the food-based Lactococcus was engineered to express CFA/I fimbriae, and Lactococcus-CFA/I fermented milk fed to arthritic mice proved highly efficacious. Protection occurred via CD39+ Tregs producing TGF-β and IL-10 to potently suppress TNF-α production and neutrophil influx into the joints. Thus, these data demonstrate the feasibility of oral nutraceuticals for treating arthritis, and potency of protection against arthritis was improved relative to that obtained with Salmonella-CFA/I.
authors: Department of Infectious Diseases & Pathology, University of Florida, Gainesville, Florida, 32611, United States of America.
authors: Massimo
authors: M
authors: Maddaloni
authors: Department of Microbiology & Immunology, Montana State University, Bozeman, Montana, 59717, United States of America.
authors: Irina
authors: I
authors: Kochetkova
authors: Department of Infectious Diseases & Pathology, University of Florida, Gainesville, Florida, 32611, United States of America.
authors: SangMu
authors: S
authors: Jun
authors: Department of Microbiology & Immunology, Montana State University, Bozeman, Montana, 59717, United States of America.
authors: Gayle
authors: G
authors: Callis
authors: Department of Microbiology & Immunology, Montana State University, Bozeman, Montana, 59717, United States of America.
authors: Theresa
authors: T
authors: Thornburg
authors: Department of Infectious Diseases & Pathology, University of Florida, Gainesville, Florida, 32611, United States of America.
authors: David W
authors: DW
authors: Pascual
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001081:Apyrase / Q000378:metabolism*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D024201:Bystander Effect / Q000276:immunology; D019587:Dietary Supplements; D007108:Immune Tolerance / Q000276:immunology; D016753:Interleukin-10 / Q000378:metabolism*; D051379:Mice; D008892:Milk / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D015703:Antigens, CD; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D001081:Apyrase; C067869:CD39 antigen
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