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.

CONCLUSION:

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: Shoichi Hoshino, Akiko Kurishima, Muneo Inaba, Yugo Ando, Toshiro Fukui, Kazushige Uchida, Akiyoshi Nishio, Hiroshi Iwai, Takashi Yokoi, Tomoki Ito, Sanae Hasegawa-Ishii, Atsuyoshi Shimada, Ming Li, Kazuichi Okazaki, Susumu Ikehara
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 46 Issue 12 Pg. 1368-81 (Dec 2011) ISSN: 1435-5922 [Electronic] Japan
• PMID: 21922185 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Pirb protein, mouse
• Receptors, Immunologic
• Trinitrobenzenesulfonic Acid

Topics

• Animals
• Colitis (immunology, pathology, therapy)
• Dendritic Cells (immunology)
• Disease Models, Animal
• Flow Cytometry
• Ileitis (immunology, pathology, therapy)
• Inflammation (immunology, pathology)
• Mice
• Mice, Inbred BALB C
• Receptors, Immunologic (immunology)
• Reverse Transcriptase Polymerase Chain Reaction
• Trinitrobenzenesulfonic Acid (toxicity)