Amelioration of 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice by immunoregulatory dendritic cells

Shoichi Hoshino, Akiko Kurishima, Muneo Inaba, Yugo Ando, Toshiro Fukui, Kazushige Uchida, Akiyoshi Nishio, Hiroshi Iwai, Takashi Yokoi, Tomoki Ito, Sanae Ishii, Atsuyoshi Shimada, Ming Li, Kazuichi Okazaki, Susumu Ikehara

Research output: Contribution to journalArticle

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Abstract

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. 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. We observed three DC subsets (PIR-A/Bhigh, PIR-A/Bmed, 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/Bmed 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/Bmed cDCs were transferred, indicating that the therapeutic ability of PIR-A/Bmed cDCs is partially dependent on IDO. The PIR-A/Bmed cDCs, which increase in number during the final stages of inflammation, can be used to treat colitis via an IDO-dependent mechanism.

Original languageEnglish (US)
Pages (from-to)1368-1381
Number of pages14
JournalJournal of Gastroenterology
Volume46
Issue number12
DOIs
StatePublished - Jan 1 2011

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Sulfonic Acids
Colitis
Dendritic Cells
Indoleamine-Pyrrole 2,3,-Dioxygenase
Immunoglobulins
Flow Cytometry
Ileitis
Self Tolerance
sym-trinitrobenzene
Adaptive Immunity
Lymphoid Tissue
Inflammatory Bowel Diseases
Small Intestine
Colon
Inflammation
Polymerase Chain Reaction
Therapeutics

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Hoshino, Shoichi ; Kurishima, Akiko ; Inaba, Muneo ; Ando, Yugo ; Fukui, Toshiro ; Uchida, Kazushige ; Nishio, Akiyoshi ; Iwai, Hiroshi ; Yokoi, Takashi ; Ito, Tomoki ; Ishii, Sanae ; Shimada, Atsuyoshi ; Li, Ming ; Okazaki, Kazuichi ; Ikehara, Susumu. / Amelioration of 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice by immunoregulatory dendritic cells. In: Journal of Gastroenterology. 2011 ; Vol. 46, No. 12. pp. 1368-1381.
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abstract = "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. 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. We observed three DC subsets (PIR-A/Bhigh, PIR-A/Bmed, 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/Bmed 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/Bmed cDCs were transferred, indicating that the therapeutic ability of PIR-A/Bmed cDCs is partially dependent on IDO. The PIR-A/Bmed cDCs, which increase in number during the final stages of inflammation, can be used to treat colitis via an IDO-dependent mechanism.",
author = "Shoichi Hoshino and Akiko Kurishima and Muneo Inaba and Yugo Ando and Toshiro Fukui and Kazushige Uchida and Akiyoshi Nishio and Hiroshi Iwai and Takashi Yokoi and Tomoki Ito and Sanae Ishii and Atsuyoshi Shimada and Ming Li and Kazuichi Okazaki and Susumu Ikehara",
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Hoshino, S, Kurishima, A, Inaba, M, Ando, Y, Fukui, T, Uchida, K, Nishio, A, Iwai, H, Yokoi, T, Ito, T, Ishii, S, Shimada, A, Li, M, Okazaki, K & Ikehara, S 2011, 'Amelioration of 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice by immunoregulatory dendritic cells', Journal of Gastroenterology, vol. 46, no. 12, pp. 1368-1381. https://doi.org/10.1007/s00535-011-0460-4

Amelioration of 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice by immunoregulatory dendritic cells. / Hoshino, Shoichi; Kurishima, Akiko; Inaba, Muneo; Ando, Yugo; Fukui, Toshiro; Uchida, Kazushige; Nishio, Akiyoshi; Iwai, Hiroshi; Yokoi, Takashi; Ito, Tomoki; Ishii, Sanae; Shimada, Atsuyoshi; Li, Ming; Okazaki, Kazuichi; Ikehara, Susumu.

In: Journal of Gastroenterology, Vol. 46, No. 12, 01.01.2011, p. 1368-1381.

Research output: Contribution to journalArticle

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T1 - Amelioration of 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice by immunoregulatory dendritic cells

AU - Hoshino, Shoichi

AU - Kurishima, Akiko

AU - Inaba, Muneo

AU - Ando, Yugo

AU - Fukui, Toshiro

AU - Uchida, Kazushige

AU - Nishio, Akiyoshi

AU - Iwai, Hiroshi

AU - Yokoi, Takashi

AU - Ito, Tomoki

AU - Ishii, Sanae

AU - Shimada, Atsuyoshi

AU - Li, Ming

AU - Okazaki, Kazuichi

AU - Ikehara, Susumu

PY - 2011/1/1

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N2 - 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. 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. We observed three DC subsets (PIR-A/Bhigh, PIR-A/Bmed, 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/Bmed 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/Bmed cDCs were transferred, indicating that the therapeutic ability of PIR-A/Bmed cDCs is partially dependent on IDO. The PIR-A/Bmed cDCs, which increase in number during the final stages of inflammation, can be used to treat colitis via an IDO-dependent mechanism.

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