S Ikehara

Kansai Medical University, Moriguchi, Ōsaka, Japan

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Publications (429)1859.19 Total impact

  • Ming Li, Kuquan Guo, Susumu Ikehara
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    ABSTRACT: Bone marrow transplantation (BMT) is used to treat hematological disorders, autoimmune diseases (ADs) and lymphoid cancers. Intra bone marrow-BMT (IBM-BMT) has been proven to be a powerful strategy for allogeneic BMT due to the rapid hematopoietic recovery and the complete restoration of T cell functions. IBM-BMT not only replaces hematopoietic stem cells (HSCs) but also mesenchymal stromal cells (MSCs). MSCs are multi-potent stem cells that can be isolated from bone marrow (BM), umbilical cord blood (UCB), and adipose tissue. MSCs play an important role in the support of hematopoiesis, and modify and influence the innate and adaptive immune systems. MSCs also differentiate into mesodermal, endodermal and ectodermal lineage cells to repair tissues. This review aims to summarize the functions of BM-derived-MSCs, and the treatment of intractable diseases such as rheumatoid arthritis (RA) and malignant tumors with IBM-BMT.
    Frontiers in Cell and Developmental Biology 09/2014; 2:48.
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    ABSTRACT: Other than that in the duodenum, adenocarcinoma in the small bowel is rare. The present study describes a case of adenocarcinoma with adenoma in the jejunum. A 70-year-old male was admitted to hospital due to dehydration induced by abdominal discomfort and difficulty with oral intake. Computed tomography revealed a tumor in the upper side of the jejunum, which was subsequently resected. The tumor contained adenocarcinoma and adenoma. The protein expression of p53 and Ki-67 was analyzed in the normal mucosa, adenoma and adenocarcinoma. The number of epithelial cells expressing p53 and Ki-67 was found to increase in the adenoma tissue compared with that in the normal mucosa. In the adenocarcinoma tissue, the number of cells expressing p53 and Ki-67 further increased, suggesting that an adenoma-adenocarcinoma sequence may occur in the small bowel, similar to that observed in the large bowel.
    Oncology letters 08/2014; 8(2):633-636. · 0.24 Impact Factor
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    ABSTRACT: Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of B-cell lymphoma characterized by selective growth of clonal B-cells in the lumen of the small vessels of various organs including the liver, spleen, lungs, skin, brain, and kidney. An 86-year-old male presented with weight loss, fever and night sweats (known as B symptoms). Blood examination revealed pancytopenia, high lactate dehydrogenase and high soluble interleukin-2 receptor, suggesting hematopoietic malignancy. However, there were no abnormal hematopoietic cells in the peripheral blood. No lymph node swelling was identified on examination by whole-body computed tomography scan. Therefore, IVLBCL was suspected, and random skin biopsies and a skin biopsy from a senile hemangioma were carried out. A small number of large atypical lymphoid cells resided in the small blood vessels in the deep dermis and subcutaneous tissue of the random skin biopsies, and numerous atypical lymphoid cells were identified in the small vessels of the senile hemangioma. These results suggest the usefulness of skin biopsy from senile hemangiomas in the diagnosis of IVLBCL.
    Oncology letters 06/2014; 7(6):2003-2006. · 0.24 Impact Factor
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    ABSTRACT: Pulmonary sclerosing hemangioma (SH) is an uncommon benign or low-grade malignant tumor. Multicentric SH and SH with lymph node metastasis have rarely been reported. The present report describes a case of pulmonary SH with lymph node metastasis in a middle-aged female. A nodule was found incidentally in the lower left lung. The patient underwent left lower pulmonary lobectomy and lymph node dissection. Histologically, the nodule demonstrated the characteristic features of SH and one of the resected lymph nodes contained a metastasis of this tumor. Thus, pulmonary SH has the potential to metastasize, a potential not suggested by histological features.
    Oncology letters 04/2014; 7(4):997-1000. · 0.24 Impact Factor
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    ABSTRACT: It has been shown that allogeneic intra-bone marrow-bone marrow transplantation (IBM-BMT) plus thymus transplantation (TT) is effective in treating recipients with malignant tumors. Although TT increases the percentage of T cells in the early term after BMT, the myeloid-derived suppressor cells (MDSCs) are still the dominant population. We used the Gr-1 Ab to deplete the granulocytic MDSCs (G-MDSCs) in tumor-bearing mice that had received BMT+TT. Two weeks after the BMT, the mice injected with Gr-1 Ab showed smaller tumors than those in the control group. In addition, Gr-1 Ab significantly increased the percentages and numbers of CD4+ and CD8+ T cells, and decreased the percentages and numbers of MDSCs and G-MDSCs. No side effects of the Gr-1 Ab on recipient or donor thymus were observed. These findings indicate that Gr-1 Ab administered after BMT+TT may enhance the effectiveness of tumor suppression.
    PLoS ONE 01/2014; 9(5):e97908. · 3.53 Impact Factor
  • Ming Li, Kequan Guo, Susumu Ikehara
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    ABSTRACT: Alzheimer's disease (AD) is a progressive and neurodegenerative disorder that induces dementia in older people. It was first reported in 1907 by Alois Alzheimer, who characterized the disease as causing memory loss and cognitive impairment. Pathologic characteristics of AD are β-amyloid plaques, neurofibrillary tangles and neurodegeneration. Current therapies only target the relief of symptoms using various drugs, and do not cure the disease. Recently, stem cell therapy has been shown to be a potential approach to various diseases, including neurodegenerative disorders, and in this review, we focus on stem cell therapies for AD.
    International Journal of Molecular Sciences 01/2014; 15(10):19226-19238. · 2.46 Impact Factor
  • Kequan Guo, Susumu Ikehara, Xu Meng
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    ABSTRACT: Organ transplantation is useful for treating the end stage of organ failure. The induction of tolerance to the transplanted organ is essential for its long-term survival. Immunologic tolerance can be induced by immunosuppressive agents and mixed chimerism. Mixed chimerism is a state in which both recipient-and donor-derived blood cells remain in the hematopoietic system after allogeneic hematopoietic stem cells have been transplanted. Mesenchymal stem cells (MSCs), and immune cells such as dendritic cells and T-reg cells play an important role in the induction of tolerance. MSCs secrete cytokines, which modulate the immune response. In particular, they upregulate T-reg cell function and thereby induce tolerance. Intra-bone marrow-bone marrow transplantation recruits both donor-derived HSCs and MSCs, inducing persistent donor-specific tolerance without the use of immunosuppressants. In this review, we summarize the use of MSCs to induce tolerance in organ transplantation.
    Frontiers in Cell and Developmental Biology 01/2014; 2:8.
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    ABSTRACT: SKG/Jcl (SKG) mice spontaneously develop T cell-mediated autoimmune arthritis and may be an effective model for studying human rheumatoid arthritis. We sought to confirm that arthritis in SKG mice was caused by stem cell disorders. We induced systemic arthritis in normal C57/BL6 (B6) mice (H-2(b) type) by injecting lineage-negative (lin(-)) immature cells isolated from bone marrow cells (BMCs) of SKG mice (H-2(d) type) directly into bone cavities. Twenty weeks later, we analyzed arthritis scores, hematoxylin-eosin (H-E) staining and tartrate-resistant acid phosphatase (TRAP) staining in ankle joints, H-2 type of hematolymphoid and osteoblast-like cells, serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and percentages of CD4(+) T cells and osteoblast-like cells expressing receptor activator of nuclear factor kappa-B ligand (RANKL) in recipient mice. Donor-derived hematolymphoid cells and osteoblast-like cells had completely replaced donor-derived cells in the recipients (H-2(b) to H-2(d)). All recipients showed severe joint swelling with hyperemia and developed hypertrophic synovitis with lymphocytes accumulated around joints. All recipients also had higher TNF-α and IL-6 levels than untreated B6 controls. Furthermore, the percentages of CD4(+) T cells and osteoblast-like cells expressing RANKL and the number of TRAP(+) cells were greater in treated animals. Donor-derived hematolymphoid cells and osteoblast-like cells persisted in these recipients and promoted autoimmune arthritis and an increase in osteoclasts. Because autoimmune arthritis may be associated with abnormal lin(-) immature cells, patients with intractable autoimmune arthritis may be treated by replacing these cells with direct injection of lin(-) immature cells isolated from normal BMCs.
    Biological & Pharmaceutical Bulletin 01/2014; 37(11):1719-26. · 1.85 Impact Factor
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    ABSTRACT: Background/Aims: Minimal-change nephrotic syndrome (MCNS) is a kidney disease defined by selective proteinuria and hypoalbuminemia occurring in the absence of cellular glomerular infiltrates or immunoglobulin deposits. Recent observations suggest that nuclear factor κB (NF-κB) of podocyte is strongly associated with the development of proteinuria in MCNS. Dehydroxymethylepoxyquinomicin (DHMEQ) is a novel NF-κB inhibitor that potently inhibits DNA-binding activity of NF-κB, resulting in several therapeutic effects in various pathological conditions. We conducted this study to ask whether DHMEQ may ameliorate the nephrosis in mice induced by puromycin aminonucleoside (PAN), which is considered to be an animal model for MCNS. Methods/Results: Pretreatment with DHMEQ alleviated the proteinuria and reversed the serum abnormalities in mice nephrosis induced by 450 mg/kg of PAN. Increased serum interleukin-6 level in PAN-induced nephrosis was also completely suppressed by DHMEQ. Electron microscopic analyses of glo-meruli indicated that DHMEQ can inhibit the podocyte foot process effacement via blocking the translocation of podocyte NF-κB from cytoplasm to nucleus. Conclusions: These results suggest that DHMEQ can be a potential therapeutic agent for MCNS.
    American Journal of Nephrology 03/2013; 37(4):302-309. · 2.62 Impact Factor
  • Ming Li, Ming Shi, Nader G Abraham, Susumu Ikehara
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    ABSTRACT: Aging is accompanied by various forms of immune dysfunction, leading to an increase in frequency of infections and the development of malignant tumors in mice and humans. Sirt1 has been implicated in processes as varied as metabolism, differentiation, cancer, and the stress response and aging. Senescence accelerated mice prone 10 (SAMP10) show not only spontaneously-occurring brain atrophy, with deficits in learning and memory, but also emotional disorders. We attempted in this study to clarify the deficits and found that the percentage of CD4/TNFα T cells in the spleen of 24-wk-old (but not 6-wk-old) SAMP10 to be significantly reduced. The thymus was significantly lighter and the percentage of CD4⁺CD8⁺ cells was significantly lower in the 24-wk-old SAMP10 than 6-wk-old SAMP10. Microarray analyses indicated that genes related to transcription coactivator activity, growth factor activity, hormone activity and cytokine activity, receptor activity, and regulation of the immune system were downregulated in the thymus of 24-wk-old SAMP10. Real time PCR analysis showed that the expression of KGF, Aire and Sirt1 was decreased on the thymic epithelial cells (TECs) of 24-wk-old SAMP10. However, these parameters improved after the mice were treated with intra-bone marrow-bone marrow transplantation. This is the first report of age-related changes in immune system dysfunction in 24-wk-old SAMP10, and the first to show that dysfunction on the TECs of 24-wk-old SAMP10 was modulated by allogeneic bone marrow cells.
    Cell Transplantation 02/2013; · 4.42 Impact Factor
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    ABSTRACT: Thymus transplantation, in conjunction with bone marrow transplantation (BMT), has been attracting attention for the treatment of various diseases. Recently, donor lymphocyte infusion (DLI) has been used as a helpful tool for establishing donor chimerism and preventing a relapse of leukemia/lymphoma. However, the effects of DLI on transplanted and recipient thymuses have not been explored. We therefore performed DLI in the intrabone marrow-BMT + thymus transplantation setting. We have found that DLI leads to derangements in both recipient thymuses and transplanted thymuses; by 2 wk after BMT, we saw a decrease in total cell number, a lower percentage of CD4(+)CD8(+) cells, and the obliteration of the thymic corticomedullary junction. Four weeks later, the thymic impairment became more serious. However, when we depleted the CD4(+) T cells (CD4(-)-DLI), the recipient thymic recovery and transplanted thymic development were significantly restored by the treatment. In addition, there were much greater levels of TNF-α and Fas ligand, and a lower percentage of regulatory T cells in the DLI group than in the CD4(-)-DLI group. These findings indicate that inflammation induced by DLI, especially by CD4(+) T cells, plays a crucial role in the thymic impairment.
    The Journal of Immunology 02/2013; · 5.52 Impact Factor
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    Ming Li, Susumu Ikehara
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    ABSTRACT: Mesenchymal stem cells (MSCs) are prototypical adult stem cells with the capacity for self-renewal and differentiation with a broad tissue distribution. MSCs not only differentiate into types of cells of mesodermal lineage but also into endodermal and ectodermal lineages such as bone, fat, cartilage and cardiomyocytes, endothelial cells, lung epithelial cells, hepatocytes, neurons, and pancreatic islets. MSCs have been identified as an adherent, fibroblast-like population and can be isolated from different adult tissues, including bone marrow (BM), umbilical cord, skeletal muscle, and adipose tissue. MSCs secrete factors, including IL-6, M-CSF, IL-10, HGF, and PGE2, that promote tissue repair, stimulate proliferation and differentiation of endogenous tissue progenitors, and decrease inflammatory and immune reactions. In this paper, we focus on the role of BM-derived MSCs in organ repair.
    Stem cells international. 01/2013; 2013:132642.
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    Ming Li, Susumu Ikehara
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    ABSTRACT: Diabetes mellitus (DM) is a group of metabolic diseases in which a person has high blood glucose levels resulting from defects in insulin secretion and insulin action. The chronic hyperglycemia damages the eyes, kidneys, nerves, heart, and blood vessels. Curative therapies mainly include diet, insulin, and oral hypoglycemic agents. However, these therapies fail to maintain blood glucose levels in the normal range all the time. Although pancreas or islet-cell transplantation achieves better glucose control, a major obstacle is the shortage of donor organs. Recently, research has focused on stem cells which can be classified into embryonic stem cells (ESCs) and tissue stem cells (TSCs) to generate functional β cells. TSCs include the bone-marrow-, liver-, and pancreas-derived stem cells. In this review, we focus on treatment using bone marrow stem cells for type 1 and 2 DM.
    Journal of Diabetes Research 01/2013; 2013:329596. · 3.54 Impact Factor
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    ABSTRACT: For immunodeficient patients, fungi are life-threatening pathogens. In this paper, we present an autopsy case of combined zygomycosis and aspergillosis. A female in her 70s on chronic hemodialysis was admitted to a hospital suffering bloody sputum, dyspnea, and fever, probably due to perinuclear anti-neutrophil cytoplasmic antibody-related vasculitis. Antibiotics were administered and immunosuppressive therapy was started, resulting in an improvement in her condition. Pneumonia later developed, followed by pulmonary bleeding and intractable pneumothorax from which she ultimately died. On autopsy, the upper lobe of the left lung was found to have hemorrhagic necrosis and showed a large longitudinal fissure. Microscopically, Zygomycota were observed in both the lungs and heart, while Aspergillus was found in the middle lobe of the right lung. Zygomycosis, which usually has a poor prognosis, is assumed to have induced hemorrhagic infarction of the lungs, inducing pulmonary bleeding and necrosis, despite the use of lipid formulations of amphotericin B, which are effective medicines against Zygomycota.
    International Journal of General Medicine 01/2013; 6:575-9.
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    ABSTRACT: Although the immune system modulates higher functions of the brain under non-inflammatory conditions, how immune cells interact with brain parenchymal cells remains to be determined. Using bone marrow chimeric mice in which the recipients' immune system was reconstituted by marrow cells derived from GFP-transgenic mice by syngeneic intra-bone marrow-bone marrow transplantation (IBM-BMT) and by intravenous (IV)-BMT, we examined the distribution, density and differentiation of donor-derived marrow cells in the brain parenchyma 2 weeks and 1, 4 and 8 months after BMT. Marrow-derived cells populated discrete brain regions from 1 to 4 months after BMT, exhibited ramified morphology and expressed Iba-1. The ramified marrow-derived cells were distributed in more brain regions and for a longer time after IBM-BMT than IV-BMT. Most of these discrete regions were adjacent to the attachments of choroid plexus that comprised thinned brain parenchyma consisting of astroglial processes in the narrow channel between the ependyma and pia. These specific portions of astroglial processes expressed fractalkine. In the choroid plexus stroma, not only myeloid cells but also CXCL12-expressing cells were of bone marrow-origin. Transcripts of fractalkine, CXCL12 and their related molecules such as CX3CR1, ADAM10 and CXCR4 were detected in the tissue consisting of the choroid plexus, the attachments and adjacent brain parenchyma. Thus, bone marrow cells selectively enter the discrete brain regions adjacent to the attachments of choroid plexus and differentiate into ramified myeloid cells. Fractalkine in the attachments of choroid plexus and CXCL12 in the choroid plexus stroma may be involved in these brain-immune interactions.
    Brain Behavior and Immunity 12/2012; · 5.61 Impact Factor
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    ABSTRACT: Thymocyte trafficking has an important role in thymic selection. Here we show that the Hippo homologue Mst1 is required for thymocyte migration and antigen recognition by LFA-1 and ICAM-1 within the medulla. Using two-photon imaging of thymic tissues, we found that highly motile mature thymocytes arrest and are activated in the vicinity of rare populations of Aire(+) ICAM-1(hi) medullary thymic epithelia in a negatively selecting environment. Notably, Mst1 deficiency or blocking the cell adhesion molecules LFA-1 and ICAM-1 results in inefficient migration and antigen recognition of CD4(+) thymocytes within the medulla. Consistent with these defects, thymocyte selection is impaired in Mst1(-/-) mice, which display T cell-dependent inflammatory infiltrates in multiple organs and develop autoantibodies. Our results suggest that Mst1 has a key role in regulating thymocyte self-antigen recognition in the medulla.
    Nature Communications 10/2012; 3:1098. · 10.74 Impact Factor
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    ABSTRACT: Purpose: It has been reported that granulocyte colony-stimulating factor (G-CSF) provides neuroprotection in models in which neuronal cell death is induced. This research was designed to investigate the effects of G-CSF on neurodegeneration of the inner retinal layer in a rat model of ischemic reperfusion (I/R) injury. Materials and Methods: Retinal ischemia was induced by increasing the intraocular pressure to 110 mm Hg for 45 min in the left eyes of the rats. A sham operation was carried out on the right eyes. G-CSF (100 µg/kg/day in 0.3 ml saline) or the same volume of saline was intraperitoneally injected just before the operation and continued for 4 consecutive days (a total of 5 consecutive days). Morphological examinations, including the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, were performed 7 days after I/R induction. The expression of phosphorylated AKT in the retina was examined by Western blot analysis and immunohistochemistry. Results: Cell loss in the ganglion cell layer was more significantly reduced in the I/R-induced eyes of the G-CSF-injected rats than in the I/R-induced eyes of the saline-injected rats (20.3 vs. 6.6%). The inner retinal thickness ratios, such as the inner plexiform layer to the inner limiting membrane/outer nuclear layer and the inner nuclear layer/outer nuclear layer, were significantly better preserved in the I/R-induced eyes of the G-CSF-injected rats than in the I/R-induced eyes of the saline-injected rats. TUNEL assays showed fewer apoptotic cells in the retinal sections of the I/R-induced eyes of the G-CSF-injected rats. The phosphorylation of AKT (p-AKT/AKT) was upregulated in the retinas of the I/R-induced eyes of the G-CSF-injected rats. Conclusion: Our results demonstrated that systemic injection of G-CSF can protect retinal ganglion cells and inner retinal layers from I/R injury. The effects could be associated with the activation of AKT.
    Ophthalmic Research 08/2012; 48(4):199-207. · 1.56 Impact Factor
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    ABSTRACT: Intra bone marrow-bone marrow transplantation (IBM- BMT) + thymus transplantation (TT) has been shown to reduce the incidence of graft versus host disease (GVHD) and restore donor-derived T cell function. In addition, an increase in insulin sensitivity occurred in db/db mice after IBM-BMT+TT treatment. Heme oxygenase (HO)-1 is a stress inducible enzyme which exert antioxidant, antiapoptotic, and immune-modulating properties. We examined whether IBM-BMT+TT could modulate the expression of HO-1 in the kidneys of db/db mice. Six-week-old db/db mice with blood glucose levels higher than 250 mg/dl were treated with IBM-BMT+TT. Six weeks later, the db/db mice showed decreased body weight, blood glucose levels and insulin, and increased plasma adiponectin levels. The upregulation of HO-1 was associated with significantly (p<0.05) increased levels of peNOS and pAKT, but decreased levels of iNOS in the kidneys of db/db mice. Plasma creatinine levels also decreased (p<0.05), and the expression of type IV collagen was improved. Thus IBM-BMT+TT unregulated the expression of HO-1, peNOS and pAKT, while decreasing iNOS levels in the kidney of db/db mice. This was associated with an improvement in renal function.
    International journal of biological sciences 01/2012; 8(10):1335-44. · 3.17 Impact Factor
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    ABSTRACT: Dehydroxymethylepoxyquinomicin (DHMEQ), a new nuclear factor (NF)-κB inhibitor, has several beneficial effects, including the suppression of tumour growth and anti-inflammatory effects. DHMEQ can also suppress the production of tumour necrosis factor (TNF)-α induced by lipopolysaccharide (LPS) in vitro. In the present study, we examine the effects of DHMEQ on TNF-α production in vivo and on the survival of mice injected with LPS. When DHMEQ was injected into mice 2 h before LPS injection, the survival of the LPS-injected mice was prolonged. When DHMEQ was injected twice (2 h before LPS injection and the day after LPS injection), all the mice were rescued. The injection of DHMEQ 1 h after LPS injection and the day after LPS injection also resulted in the rescue of all mice. The serum levels of TNF-α in the mice that received both LPS and DHMEQ were suppressed compared to the mice that received only LPS. These results suggest that DHMEQ can be utilized for the prevention and treatment of endotoxin shock.
    Clinical & Experimental Immunology 11/2011; 166(2):299-306. · 3.41 Impact Factor
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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/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. 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.
    Journal of Gastroenterology 09/2011; 46(12):1368-81. · 3.79 Impact Factor

Publication Stats

10k Citations
1,859.19 Total Impact Points


  • 1987–2014
    • Kansai Medical University
      • • Department of Ophthalmology
      • • Department of Otolaryngology
      • • Department of Orthopaedic Surgery
      Moriguchi, Ōsaka, Japan
  • 2012
    • Aichi Human Service Center
      Касугай, Aichi, Japan
  • 2007–2011
    • Nanfang Hospital
      Shengcheng, Guangdong, China
  • 2004–2010
    • Osaka Prefecture University
      • Graduate School of Life and Environmental Sciences
      Sakai, Osaka-fu, Japan
  • 2009
    • University of Toledo
      • Department of Physiology and Pharmacology
      Toledo, OH, United States
  • 1984–2009
    • Kyoto University
      • • Department of Zoology
      • • Graduate School of Medicine / Faculty of Medicine
      • • Department of Cardiovascular Medicine
      • • Department of Dermatology
      Kioto, Kyōto, Japan
  • 2008
    • Ibaraki Children's Hospital
      Ibaragi, Ōsaka, Japan
    • Università di Pisa
      • Department of Biology
      Pisa, Tuscany, Italy
  • 2002–2008
    • Kyoto Institute of Technology
      Kioto, Kyōto, Japan
    • New York Medical College
      • • Department of Medicine
      • • Department of Pharmacology
      New York City, NY, United States
  • 2002–2006
    • University of California, Davis
      • Division of Rheumatology/Allergy/Clinical Immunology
      Davis, CA, United States
  • 1990–2004
    • Kyoto Prefectural University of Medicine
      • Graduate School of Medical Science
      Kioto, Kyōto, Japan
  • 1989–2002
    • University of South Florida
      • Department of Pediatrics
      Tampa, FL, United States
  • 1995
    • University of South Florida St. Petersburg
      St. Petersburg, Florida, United States
    • University of Ulsan
      • Asan Medical Center
      Ulsan, Ulsan, South Korea
  • 1994
    • Asan Medical Center
      • Department of Pathology
      Seoul, Seoul, South Korea
  • 1992–1993
    • Osaka Red Cross Hospital
      Ōsaka, Ōsaka, Japan
  • 1991
    • Hokkaido University
      • Institute of Immunological Science
      Sapporo, Hokkaidō, Japan
    • All Children's Hospital
      Florida City, Florida, United States
  • 1981–1983
    • Memorial Sloan-Kettering Cancer Center
      New York City, New York, United States