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



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 CD4CD25 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 CD103CD11c dendritic cells and regulatory T cells (Tregs).



We identified 4 candidate epitope peptides of CA I. Among these, Reg-DCs pulsed with CA I 58-73 peptide (Reg-DCsCA I 58-73) alone ameliorated colitis. Reg-DCsCA 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 Foxp3CD4CD25 Tregs and CD103CD11c dendritic cells in MLNs and colon. Administration of Reg-DCsCA I 58-73 induced antigen-specific Tregs in MLNs of colitic mice.



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.
Departments of *Gastroenterology and Metabology, and†Immunology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Sen
S
Yagi
Masanori
M
Abe
Masakatsu
M
Yamashita
Kenichirou
K
Mori
Hirofumi
H
Yamanishi
Eiji
E
Arimitsu
Yasunori
Y
Yamamoto
Eiji
E
Takeshita
Yoshio
Y
Ikeda
Yoichi
Y
Hiasa
D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D024401:Carbonic Anhydrase I / Q000276:immunology / Q000627:therapeutic use*; D003092:Colitis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D000939:Epitopes / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D039001:Integrin alpha Chains / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics; D020381:Interleukin-17 / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics; D010455:Peptides / Q000276:immunology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism*; D050697:Retinal Dehydrogenase; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics
D015703:Antigens, CD; D039521:CD11c Antigen; D015704:CD4 Antigens; D000939:Epitopes; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C556062:IL10 protein, mouse; C098680:Il17a protein, mouse; D039001:Integrin alpha Chains; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D010455:Peptides; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C091367:alpha E integrins; D016753:Interleukin-10; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C512722:Aldh1a2 protein, mouse; D050697:Retinal Dehydrogenase; D024401:Carbonic Anhydrase I