PMID- 29508072 OWN - NLM STAT- MEDLINE DCOM- 20190802 LR - 20190802 IS - 1435-5922 (Electronic) IS - 0944-1174 (Linking) VI - 53 IP - 10 DP - 2018 Oct TI - Induction of PIR-A/B(+) DCs in the in vitro inflammatory condition and their immunoregulatory function. PG - 1131-1141 LID - 10.1007/s00535-018-1447-1 [doi] AB - BACKGROUND: Dendritic cells (DCs), primary antigen-presenting cells, are now well known as an immunoregulator of many aspects of immune responses including inflammatory bowel diseases (IBDs) such as Crohn's disease and ulcerative colitis. We have reported that PIR-A/B(high) cDCs (conventional DCs) appeared in dextran sodium sulfate (DSS)-induced colitis and serve as a negative immunoregulator in an animal model of IBD. The immunoregulatory role of PIR-A/B(+) cDCs was confirmed in both an in vitro culture system and an in vivo transfer experiment. Here, we have investigated the differentiation process of PIR-A/B(+) cDCs in an in vitro inflammatory environment and examined their functions. METHODS: cDCs were isolated from the large intestinal lamina propria from C57BL/6 mice and cultured in an inflammatory environment (IL-1, IL-6, TNFalpha, and LPS). The appearance of PIR-A/B(+) cDCs was determined after 24 h, and the in vitro-induced PIR-A/B(+) cDCs were functionally and genetically examined. RESULTS: PIR-A/B(+) cDCs were detected after a 24-h culture only in the inflammatory environment, and the cells acted as a negative immunoregulator when examined in an allogenic mixed leukocyte reaction (MLR). The message level of IL-27 was highly upregulated in PIR-A/B(+) cDCs, while that of high mobility group box 1 protein (HMGB1) was downregulated in these cells. This was well in accordance with the fact that PIR-A/B(+) cDCs showed a suppressive function against activated T cells. We found that PIR-A/B(+) cDCs produced IL-27, as verified by an ELISA assay, and that the inhibitory effect by PIR-A/B(+) cDCs was, at least partially, due to IL-27. Furthermore, CD85d(+) cells, a human counterpart of mouse PIR-A/B(+) cDCs, were found in the lamina propria of the colon of the patients with ulcerative colitis, but not in the similar part of the non-inflammatory area of colon specimens from patients with colon cancer. CONCLUSIONS: PIR-A/B(+) cDCs induced in an in vitro inflammatory environment model showed a suppressive function against activated T cells by producing an inhibitory cytokine. FAU - Matsui, Fumi AU - Matsui F AD - Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1191, Japan. FAU - Inaba, Muneo AU - Inaba M AD - First Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, Japan. FAU - Uchida, Kazushige AU - Uchida K AD - Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1191, Japan. FAU - Nishio, Akiyoshi AU - Nishio A AD - Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1191, Japan. FAU - Fukui, Toshiro AU - Fukui T AD - Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1191, Japan. FAU - Yoshimura, Hideaki AU - Yoshimura H AD - First Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, Japan. FAU - Satake, Atsushi AU - Satake A AD - First Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, Japan. FAU - Yoshioka, Kazuhiko AU - Yoshioka K AD - Gastrointestinal Surgery, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, Japan. FAU - Nomura, Shosaku AU - Nomura S AD - First Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, Japan. FAU - Okazaki, Kazuichi AU - Okazaki K AD - Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, 2-5-1, Shinmachi, Hirakata, Osaka, 573-1191, Japan. okazaki@hirakata.kmu.ac.jp. LA - eng PT - Journal Article DEP - 20180305 PL - Japan TA - J Gastroenterol JT - Journal of gastroenterology JID - 9430794 RN - 0 (HMGB1 Protein) RN - 0 (HMGB1 protein, mouse) RN - 0 (Il27 protein, mouse) RN - 0 (Interleukins) RN - 0 (LILRB2 protein, human) RN - 0 (Membrane Glycoproteins) RN - 0 (Pira1 protein, mouse) RN - 0 (Pirb protein, mouse) RN - 0 (Receptors, Immunologic) RN - 9042-14-2 (Dextran Sulfate) MH - Adoptive Transfer/methods MH - Animals MH - Cell Differentiation MH - Cells, Cultured MH - Colitis/chemically induced MH - Colitis, Ulcerative/chemically induced/genetics/*immunology/*physiopathology MH - Colon/cytology MH - Dendritic Cells/*immunology/metabolism MH - Dextran Sulfate/pharmacology MH - Disease Models, Animal MH - Down-Regulation MH - Female MH - Gene Expression MH - HMGB1 Protein/biosynthesis/genetics MH - Humans MH - Inflammation/*chemically induced MH - Inflammatory Bowel Diseases/metabolism/pathology MH - Interleukins/biosynthesis/genetics MH - Lymphocyte Activation MH - Lymphocyte Culture Test, Mixed/methods MH - Membrane Glycoproteins/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Receptors, Immunologic/*biosynthesis/metabolism MH - T-Lymphocytes/metabolism MH - Up-Regulation OTO - NOTNLM OT - Dendritic cells OT - IL-27 OT - In vitro differentiation process OT - Paired immunoglobulin-like receptors EDAT- 2018/03/07 06:00 MHDA- 2019/08/03 06:00 CRDT- 2018/03/07 06:00 PHST- 2017/07/27 00:00 [received] PHST- 2018/02/20 00:00 [accepted] PHST- 2018/03/07 06:00 [pubmed] PHST- 2019/08/03 06:00 [medline] PHST- 2018/03/07 06:00 [entrez] AID - 10.1007/s00535-018-1447-1 [pii] AID - 10.1007/s00535-018-1447-1 [doi] PST - ppublish SO - J Gastroenterol. 2018 Oct;53(10):1131-1141. doi: 10.1007/s00535-018-1447-1. Epub 2018 Mar 5.