Facilitated Peptide Transportviathe Mucosal Epithelium: Impact on Tolerance Induction.
A hallmark of autoimmunity is the breakdown of tolerance and generation of effector responses against self-antigens. Re-establishment of tolerance in autoimmune disorders was always the most desired treatment option; however, despite many efforts, clinical trials have been largely unsuccessful. This also applies to the generation of oral tolerance, which seems to be a default response type of the mucosa-associated lymphoid tissues to harmless antigens. In this study, we report improved efficacy of oral tolerance induction by coupling antigen with the newly identified mucosal carrier peptide 13C. Antigen coupled to 13C is efficiently taken up in the gastrointestinal tract and could be visualized in cells of the lamina propria. Oral, rectal, or nasal treatment effectively induced the proliferation of antigen-specific T cells with some increase in the frequency of regulatory T cells. In a model of delayed-type hypersensitivity, especially intrarectal tolerization treatment resulted in reduced footpad swelling, demonstrating a moderate tolerogenic effect of mucosal treatment with 13C coupled antigen. Coupling of antigens to a transmucosal carrier, therefore, is a promising tool to improve the efficacy of vaccinationviamucosal surfaces.
Experimental Rheumatology, Deutsches Rheuma-Forschungszentrum, Berlin, Germany; Rheumatology, Department of Gastroenterology, Infectiology and Rheumatology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Elisabeth E
EE
Kenngott
Experimental Rheumatology, Deutsches Rheuma-Forschungszentrum, Berlin, Germany; Experimental Rheumatology, Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Jennifer
J
Pfeil
Experimental Rheumatology, Deutsches Rheuma-Forschungszentrum , Berlin , Germany.
Ute
U
Hoffmann
Experimental Rheumatology, Deutsches Rheuma-Forschungszentrum , Berlin , Germany.
Uta
U
Lauer
Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, Research Center ImmunoSciences, Charité Universitätsmedizin Berlin , Berlin , Germany.
Anja A
AA
Kühl
Experimental Rheumatology, Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin , Berlin , Germany.
Anne
A
Rigby
The Hopkirk Research Institute, AgResearch Ltd., Grasslands Research Institute , Palmerston North , New Zealand.
Anton
A
Pernthaner
Experimental Rheumatology, Deutsches Rheuma-Forschungszentrum, Berlin, Germany; Experimental Rheumatology, Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Alf
A
Hamann
mucosa; mucosal uptake; oral tolerance; peptide vaccination; regulatory T cells; targeted delivery