Kenjiro Fujimura
Kyushu University
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Featured researches published by Kenjiro Fujimura.
The Journal of Rheumatology | 2011
Hisakata Yamada; Yasuharu Nakashima; Ken Okazaki; Taro Mawatari; Jun Ichi Fukushi; Akiko Oyamada; Kenjiro Fujimura; Yukihide Iwamoto; Yasunobu Yoshikai
Objective. It was previously found that Th1 but not Th17 cells were predominant in the joints of rheumatoid arthritis (RA). To verify whether this is a unique feature of CD4 T cells in RA joints, we performed comparative flow cytometric analysis of CD4 T cells in RA and osteoarthritis (OA) joints. Methods. Mononuclear cells were isolated from peripheral blood (PB), synovial membrane (SM), and synovial fluid (SF) from a total of 18 RA and 12 OA patients. The expression of surface molecules and cytokine production of CD4 T cells was examined by a flow cytometer. Results. Most CD4 T cells in RA joints expressed memory/activation markers, such as CD45RO, HLA-DR, and CD69. CCR5 was highly expressed on CD4 T cells in SF but not in PB or SM. With regard to Th17-related molecules, CD4 T cells expressing CCR6 were not enriched in either SF or SM. In contrast, CD161-positive cells were abundant in the joint, many of which, however, produced interferon-γ but not interleukin 17A. Virtually all T cells in OA joints, although much less numerous than in RA joints, expressed activation markers. Th1 cells were predominant in both OA and RA joints, while there were a few Th17 cells. The frequency of Th17 cells in the joint tended to be lower in OA than RA. Conclusion. There was a quantitative but not qualitative difference in CD4 T cells, including the expression of activation markers and cytokine profiles, between RA and OA joints.
Arthritis Research & Therapy | 2016
Koji Sakuraba; Akiko Oyamada; Kenjiro Fujimura; Rosanne Spolski; Yukihide Iwamoto; Warren J. Leonard; Yasunobu Yoshikai; Hisakata Yamada
BackgroundInterleukin-21 (IL-21) is a T-cell-derived cytokine whose receptor is expressed on a variety of cells and therefore might have pleiotropic roles in the pathogenesis of rheumatoid arthritis (RA). In this study, we investigated the involvement of IL-21 signaling in the development of collagen-induced arthritis (CIA), an animal model of RA, using IL-21 receptor knockout (Il21r KO) mice.MethodsIl21r KO mice or wild-type (WT) C57BL/6 mice were immunized with chicken type II collagen (CII) emulsified in complete Freund adjuvant on day 0 and were given a boost injection on day 21. The production of anti-CII antibody, development of T-cell and B-cell subsets, and T-cell responses to CII were analyzed. CIA was induced in Rag2 KO mice to which combinations of WT or Il21r KO CD4 T cells and WT or Il21r KO B cells had been transferred, in order to examine the role of IL-21 signaling in each cell subset.ResultsIl21r KO mice were resistant to the development of CIA. CII-specific IgG but not IgM production was impaired in Il21r KO mice. This is consistent with a reduction of germinal center B cells in the draining lymph nodes. In contrast, CII-specific Th1 and Th17 responses were unaffected in Il21r KO mice. There was also no difference in the number of CII-specific follicular helper T cells between WT and Il21r KO mice. By analyzing the development of CIA in T-cell and B-cell mixed transfer experiments, we confirmed that IL-21 receptor expression on B cells, but not on T cells, was essential for the development of CIA.ConclusionIL-21 signaling in B cells, but not in T cells, plays essential roles in the production of pathogenic autoantibodies that induce CIA development.
Journal of Leukocyte Biology | 2013
Kenjiro Fujimura; Akiko Oyamada; Yukihide Iwamoto; Yasunobu Yoshikai; Hisakata Yamada
IL‐2 signaling is involved in clonal expansion of antigen‐specific CD4 T cells. IL‐2 is also reported to promote Th1 but inhibit Th17 differentiation, although in vivo relevance remains unclear. In addition, IL‐2‐dependent Foxp3+ CD4 Tregs suppress T cell proliferation, complicating the in vivo role of IL‐2 in the development of Th cell responses. To elucidate the roles of cell‐intrinsic IL‐2 signaling in CD4 T cells, we cotransferred TCR‐Tg CD4 T cells from IL‐2Rα (CD25)‐deficient and WT mice and analyzed development of antigen‐specific Th1 and Th17 responses. It was revealed that Th17 development of antigen‐specific CD4 T cells was largely unaffected, whereas Th1 development was impaired by the lack of IL‐2 signaling. Similar data were obtained from mixed BM chimera experiments using BM cells from CD25‐deficient and WT mice. In addition, although in vitro blockade of IL‐2 during Th17 development greatly increased the percentages of Th17 cells, it did not affect their numbers, indicating that in vitro Th17 development is also IL‐2‐independent. Th1 development was dependent on IL‐2 in vitro as well. Thus, our data suggest that cell‐intrinsic IL‐2 signaling is critical for Th1 development but plays a limited role in Th17 development in vitro as well as in vivo.
European Journal of Immunology | 2011
Takafumi Fuchiwaki; Xun Sun; Kenjiro Fujimura; Hisakata Yamada; Kensuke Shibata; Hiromi Muta; Eckhard R. Podack; Hideyuki Kawauchi; Yasunobu Yoshikai
CD30 ligand (CD30L) plays an important role in the amplification and/or activation of effector CD4+ T cells, irrespective of Th cell subset. To examine the role of CD30L in allergic rhinitis, we evaluated an OVA model of allergic rhinitis in CD30L knock out (KO) mice on a BALB/c background sensitized with OVA. Symptoms of allergic rhinitis such as eosinophil infiltration into the nasal mucosa were drastically diminished in OVA‐sensitized CD30L KO mice following intranasal challenge with OVA. The levels of OVA‐specific IgE in the sera and the Th2 response in nasopharynx‐associated lymphoid tissues and cervical LNs of CD30L KO mice were significantly lower than those of WT mice following intranasal challenge with OVA. Intranasal administration of CD30‐Ig during the effector phase with OVA significantly prevented the development of allergic rhinitis in WT mice. These results suggest that CD30L plays an important role in allergic rhinitis and that the inhibition of CD30L/CD30 signaling might be useful as a novel biological therapy for allergic rhinitis.
Modern Rheumatology | 2017
Akihisa Haraguchi; Yasuharu Nakashima; Hisaaki Miyahara; Yukio Esaki; Ken Okazaki; Jun Ichi Fukushi; Go Hirata; Satoshi Ikemura; Satoshi Kamura; Koji Sakuraba; Kenjiro Fujimura; Yukio Akasaki; Hisakata Yamada
Abstract Objectives: To retrospectively evaluate the long-term results of cementless total hip arthroplasty (THA) in patients with rheumatoid arthritis (RA) and postoperative patient mortality after THA. Methods: This study included 191 hips in 149 RA patients who underwent cementless THA between 1998 and 2005. Mean age at surgery was 54.2 years, and mean follow-up was 12.6 years. Implant and patient survivorships were determined using the Kaplan–Meier method, and the associated influencing factors were determined. Results: Implant survivals at 17 years were 99.5% for stems, 93.9% for cups, and 90.8% for liners. Among the liners used, THAs with highly cross-linked polyethylene showed better survivals compared with those with conventional polyethylene and alumina-bearing surface (93.4%, 90.9%, and 52.2%, respectively). A total of 64 deaths occurred; 45 patients died within 10 years and 19 patients died between 10 and 17 years. Malignancy (25.0%) was the leading cause of death, followed by pneumonia (20.8%) and sepsis (20.8%). The patient survival rate was 36.9% at 17 years after THA. Multivariate analysis exhibited that older age at operation and greater dose of concomitant corticosteroid resulted in shorter patient survivals. Conclusions: Cementless THA worked well in patients with RA. Mortality remained high among RA patients who needed THA.
Arthritis & Rheumatism | 2015
Koji Sakuraba; Kenjiro Fujimura; Yasuharu Nakashima; Ken Okazaki; Jun Ichi Fukushi; Masanobu Ohishi; Akiko Oyamada; Yukio Esaki; Hisaaki Miyahara; Yukihide Iwamoto; Yasunobu Yoshikai; Hisakata Yamada
To establish a method to culture synovial tissue explants from patients with rheumatoid arthritis (RA).
Modern Rheumatology Case Reports | 2018
Kenjiro Fujimura; Hiromichi Mitsuyasu; Motoko Ishida; Koji Sakuraba; Masataka Nakamura; Tomoya Miyamura; Satoshi Kamura; Eiichi Suematsu; Hisaaki Miyahara
Abstract We experienced a rare case of severe contractured and flexed metacarpophalangeal joint (MPJ) arthropathy in a patient with overlap syndrome of systemic lupus erythematosus and dermatomyositis. The patient was a 60-year-old female with high anti-nuclear antibody and anti-Jo-1 antibody titers whose hands had gradually deformed without arthralgia during the past 6 years. Both hands were extremely contractured; in particular, the right hand had dislocations of the second to fifth MPJs, ankyloses of some proximal interphalangeal and distal interphalangeal joints, and z-shaped deformity of the thumb. We performed thumb arthroplasty and artificial joint replacement of the second to fifth MPJs of the dominant right hand. These operations enabled improvement of the patient’s ability to perform daily activities, with an improvement from 1.125 to 0.625 of the Japanese version of the Stanford Health Assessment Questionnaire score. Although surgery to treat contractured deformities can only partially recover the functional ability, it also has indications for arthroplasties.
Modern Rheumatology | 2018
Toshifumi Fujiwara; Kenjiro Fujimura; Satoshi Hamai; Satoshi Kamura; Yasuharu Nakashima; Hisaaki Miyahara
Abstract Objectives: This study retrospectively investigated the mid-term outcome of Legacy constrained condylar knee (LCCK) prosthesis in patients with rheumatoid arthritis (RA) having severe varus/valgus deformity, instability, and/or bone loss. Methods: Between January 2000 and December 2015, LCCK prostheses had been performed in 32 knees of 25 patients with RA, and 23 knees of 17 patients of the postoperative follow-up minimum 2 years were analyzed in this study (Primary: 14 knees, Revision: 9 knees). The average of follow-up duration was 6.9 ± 2.7 years, all were female, and the average of age and RA duration at the surgery was 59.0 ± 9.5 years and 26.6 ± 13.5 years, respectively. Clinical result was analyzed by Knee Society Score (KSS) knee and function at preoperative time and final visit. Imaging outcome was investigated by femoral tibial angle (FTA), four component alignment angles, and radiolucent line at pre-/postoperative time. Results: KSS knee/function scores and radiographic FTAs were improved after operation. Radiolucent lines around components were seen in 17 knees (73.9%), of which only one knee (4.3%) has shown aseptic loosening. The seven-year Kaplan-Meier survivorship analysis resulted in 91.7%. Conclusion: LCCK prosthesis in RA patients was achieved to the excellent mid-term clinical and radiographic result.
Case reports in orthopedics | 2018
Kenjiro Fujimura; Koji Sakuraba; Satoshi Kamura; Kiyoshi Miyazaki; Nobuo Kobara; Kazumasa Terada; Hisaaki Miyahara
Acute rupture of the knee extensor mechanism after patellectomy is extremely rare. We present the case of a patient with acute patellar tendon rupture who had undergone patellectomy 53 years before. Twelve days after the injury, the ruptured patellar tendon was repaired with end-to-end suture. Postoperatively, we splinted the knee for 6 weeks but permitted the patient to walk without limiting weight bearing at 1 week postoperatively. At one-year follow-up, the patient is able to move his knee almost full range of motion and the Lysholm knee score is 81. The patient is satisfied with the outcome. This is the first report to treat acute rupture of the patellar tendon in a patient who had undergone patellectomy. Although careful rehabilitation is required, end-to-end suture might be an adequate surgical procedure for acute rupture of the knee extensor mechanism after patellectomy.
European Journal of Immunology | 2013
Hisakata Yamada; Kensuke Shibata; Koji Sakuraba; Kenjiro Fujimura; Yasunobu Yoshikai
In contrast to thymic epithelial cells, which induce the positive selection of conventional CD8+ T cells, hematopoietic cells (HCs) select innate CD8+ T cells whose Ag specificity is not fully understood. Here we show that CD8+ T cells expressing an H‐Y Ag‐specific Tg TCR were able to develop in mice in which only HCs expressed MHC class I, when HCs also expressed the H‐Y Ag. These HC‐selected self‐specific CD8+ T cells resemble innate CD8+ T cells in WT mice in terms of the expression of memory markers and effector functions, but are phenotypically distinct from the thymus‐independent CD8+ T‐cell population. The peripheral maintenance of H‐Y‐specific CD8+ T cells required presentation of the self‐Ag and IL‐15 on HCs. HC‐selected CD8+ T cells in mice lacking the Tg TCR also showed these features. Furthermore, by using MHC class I tetramers with a male Ag peptide, we found that self‐Ag‐specific CD8+ T cells in TCR non‐Tg mice could develop via HC‐induced positive selection, supporting results obtained from H‐Y TCR Tg mice. These findings indicate the presence of self‐specific CD8+ T cells that are positively selected by HCs in the peripheral T‐cell repertoire.