ZP3 peptides administered orally suppress murine experimental autoimmune ovarian disease

Abstract

Experimental autoimmune ovarian disease (AOD) is a T cell-mediated chronic inflammatory disease that may lead to premature ovarian failure. Autoimmune disease can be suppressed by oral administration of autoantigens leading to tolerance. One of the major mechanisms of oral tolerance is induction of regulatory CD4 + T cells that can mediate active suppression by producing immunomodulatory cytokines. However, the role of oral tolerance as a treatment for experimental AOD has received little attention. Therefore, the purpose of this study was to examine the conditions necessary to produce oral tolerance in experimental AOD in B6AF1 female mice. In this study, mice received different doses of peptides of the mouse zona pellucida 3 (pZP3) via gastric intubation for 7 times. After 4 times of oral administration, AOD was induced by immunization with pZP3. The optimal tolerating regimen for oral administration of pZP3 in mice was 10 μg, which decreased morbidity of oophoritis compared to the control group. In this moderate-dose therapeutic group (MD), alterations in the estrous cycle were normalized and CD4 + T cells that were CD25 + increased while those that were CD25 decreased. The severity of autoimmune oophoritis and the titer of ZP autoantibodies were also significantly reduced. These findings suggest that oral administration of pZP3 may be successfully used as an oral tolerance strategy for suppression of AOD.