title: Amelioration of 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice by immunoregulatory dendritic cells.
abstract: BACKGROUND
  Dendritic cells (DCs) are widely distributed throughout the lymphoid and nonlymphoid tissues, and are important initiators of acquired immunity. They also serve as regulators by inducing self-tolerance. However, it has not been thoroughly clarified whether DCs are somehow involved in the regulation or treatment of inflammatory bowel diseases.
  
  
  METHODS
  We established an ileitis model by transmurally injecting 2,4,6-trinitrobenzene sulfonic acid (TNBS) into the lumen of the ileocolonic junction. The kinetic movement of DCs at the inflammatory sites was analyzed histologically and by flow cytometry, and DCs obtained from the small intestine were analyzed in order to determine the expression of paired immunoglobulin-like receptor-A/B (PIR-A/B) by flow cytometry and quantitative RT-PCR. Furthermore, the regulatory role of DCs was directly determined by a transfer experiment using TNBS-induced colitis model mice.
  
  
  RESULTS
  We observed three DC subsets (PIR-A/B(high), PIR-A/B(med), and PIR-A/B(-) DCs) in the conventional DCs (cDCs) from day 3, and the number of PIR-A/B(med) cDCs increased from the time the inflammatory responses ceased (day 7). PIR-A/B(med) cDCs actually migrated to the inflamed colon, and ameliorated the colitis induced by TNBS when transferred to colitis-induced recipients. The colitis was greatly exacerbated when mice had been treated with the indoleamine-pyrrole 2,3-dioxygenase (IDO) inhibitor 1-methyltryptophan (1-mT) at the time PIR-A/B(med) cDCs were transferred, indicating that the therapeutic ability of PIR-A/B(med) cDCs is partially dependent on IDO.
  
  
  CONCLUSIONS
  The PIR-A/B(med) cDCs, which increase in number during the final stages of inflammation, can be used to treat colitis via an IDO-dependent mechanism.
authors.affiliation: Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, Moriguchi, Osaka, Japan. hoshinos@takii.kmu.ac.jp
authors.forename: Shoichi
authors.initials: S
authors.lastname: Hoshino
authors.forename: Akiko
authors.initials: A
authors.lastname: Kurishima
authors.forename: Muneo
authors.initials: M
authors.lastname: Inaba
authors.forename: Yugo
authors.initials: Y
authors.lastname: Ando
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fukui
authors.forename: Kazushige
authors.initials: K
authors.lastname: Uchida
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishio
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwai
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokoi
authors.forename: Tomoki
authors.initials: T
authors.lastname: Ito
authors.forename: Sanae
authors.initials: S
authors.lastname: Hasegawa-Ishii
authors.forename: Atsuyoshi
authors.initials: A
authors.lastname: Shimada
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Kazuichi
authors.initials: K
authors.lastname: Okazaki
authors.forename: Susumu
authors.initials: S
authors.lastname: Ikehara
mesh_terms: D000818:Animals; D003092:Colitis / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007079:Ileitis / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011971:Receptors, Immunologic / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
chemical_list: C105949:Pirb protein, mouse; D011971:Receptors, Immunologic; D014302:Trinitrobenzenesulfonic Acid