Carbonic Anhydrate i Epitope Peptide Improves Inflammation in a Murine Model of Inflammatory Bowel Disease

Abstract

Background: Carbonic anhydrase I (CA I), a major cecal bacterial antigen, improves inflammatory bowel disease (IBD) symptoms in a murine model. The aim of this study was to identify the responsible epitope region within the CA I protein and evaluate its effect on inflammation using a murine IBD model. Methods: Candidate peptides within the CA I protein sequence that interact with major histocompatibility complex class II were chosen and their immune responses were evaluated using mesentery lymph nodes (MLNs) from a CD4 + CD25 - T-cell transfer murine colitis model. Mice were treated with regulatory dendritic cells (Reg-DCs)-pulsed CA I peptide. We assessed their clinical signs, histopathology, induction of cytokines and transcription factors, and generation of CD103 + CD11c + dendritic cells and regulatory T cells (Tregs). Results: We identified 4 candidate epitope peptides of CA I. Among these, Reg-DCs pulsed with CA I 58-73 peptide (Reg-DCs CA I 58-73) alone ameliorated colitis. Reg-DCs CA I 58-73 -treated mice showed higher mRNA expression levels of forkhead box protein 3, aldehyde dehydrogenase family 1a2, transforming growth factor-β, and interleukin (Il)10, when compared with lower mRNA expression of retinoic acid-related orphan receptor gamma and Il17a in MLNs. Compared with control mice, these mice also showed higher numbers of Foxp3 + CD4 + CD25 + Tregs and CD103 + CD11c + dendritic cells in MLNs and colon. Administration of Reg-DCs CA I 58-73 induced antigen-specific Tregs in MLNs of colitic mice. Conclusions: CA I 58-73 peptide induces antigen-specific therapeutic effect in a murine IBD model using Reg-DCs, indicating that CA I 58-73 is a candidate epitope for IBD immunotherapy.