Autoimmune diseases arise from the loss of tolerance to self, and because the etiologies of\nsuch diseases are largely unknown, symptomatic treatments rely on anti-inflammatory and\nanalgesic agents. Tolerogenic treatments that can reverse disease are preferred, but again,\noften thwarted by not knowing the responsible auto-antigens (auto-Ags). Hence, a viable alternative\nto stimulating regulatory T cells (Tregs) is to induce bystander tolerance. Colonization\nfactor antigen I (CFA/I) has been shown to evoke bystander immunity and to hasten\nAg-specific Treg development independent of auto-Ag. To translate in treating human autoimmune\ndiseases, the food-based Lactococcus was engineered to express CFA/I fimbriae,\nand Lactococcus-CFA/I fermented milk fed to arthritic mice proved highly efficacious. Protection\noccurred via CD39+ Tregs producing TGF-? and IL-10 to potently suppress TNF-?\nproduction and neutrophil influx into the joints. Thus, these data demonstrate the feasibility\nof oral nutraceuticals for treating arthritis, and potency of protection against arthritis was improved\nrelative to that obtained with Salmonella-CFA/I.
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