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Oral therapy with colonization factor antigen I prevents development of type 1 diabetes in Non-obese Diabetic mice.

ABSTRACT: Antigen (Ag)-specific tolerization prevents type 1 diabetes (T1D) in non-obese diabetic (NOD) mice but proved less effective in humans. Several auto-Ags are fundamental to disease development, suggesting T1D etiology is heterogeneous and may limit the effectiveness of Ag-specific therapies to distinct disease endotypes. Colonization factor antigen I (CFA/I) fimbriae from Escherichia coli can inhibit autoimmune diseases in murine models by inducing bystander tolerance. To test if Ag-independent stimulation of regulatory T cells (Tregs) can prevent T1D onset, groups of NOD mice were orally treated with Lactococcus lactis (LL) expressing CFA/I. LL-CFA/I treatment beginning at 6 weeks of age reduced disease incidence by 50% (p?+CD8+ T cells 6-fold at 11 weeks (p?+CD4+ T cells were suppressed 10-fold (p?+CD4+ T cells were suppressed (p?

SUBMITTER: Nelson AS 

PROVIDER: S-EPMC7145799 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Oral therapy with colonization factor antigen I prevents development of type 1 diabetes in Non-obese Diabetic mice.

Nelson Andrew S AS   Maddaloni Massimo M   Abbott Jeffrey R JR   Hoffman Carol C   Akgul Ali A   Ohland Christina C   Gharaibeh Raad Z RZ   Jobin Christian C   Brusko Todd M TM   Pascual David W DW  

Scientific reports 20200409 1

Antigen (Ag)-specific tolerization prevents type 1 diabetes (T1D) in non-obese diabetic (NOD) mice but proved less effective in humans. Several auto-Ags are fundamental to disease development, suggesting T1D etiology is heterogeneous and may limit the effectiveness of Ag-specific therapies to distinct disease endotypes. Colonization factor antigen I (CFA/I) fimbriae from Escherichia coli can inhibit autoimmune diseases in murine models by inducing bystander tolerance. To test if Ag-independent s  ...[more]

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