The University of Tokyo · Medicine
Professor Tetsuya Hirata's research lab focuses on the immunological and molecular mechanisms underlying chronic inflammatory diseases, particularly endometriosis. The lab investigates the role of T helper 17 (Th17) cells and their cytokine IL-17A in disease pathogenesis, with a specific emphasis on chemokine-mediated migration (e.g., CCL20-CCR6 axis) and Toll-like receptor 4 (TLR4) signaling in endometrial cells. Additionally, the lab explores stem cell biology, particularly the role of Zscan4 in induced pluripotent stem cell (iPSC) reprogramming, contributing to regenerative medicine. The research integrates immunology, reproductive biology, and molecular signaling to uncover novel therapeutic targets.
Figures are computed from collected data and may differ slightly.
IL-17A is secreted from Th17 cells, a discovery leading to revision of the mechanism underlying the role of Th1/Th2 in the immune response. Strong evidence suggests that immune responses associated with inflammation are involved in the pathogenesis of endometriosis. In the present study, we first demonstrated that the presence of Th17 cells in peritoneal fluid of endometriotic women by flow cytometric analysis and IL-17A-positive cells in endometriotic tissues by immunohistochemistry. To investi
In a novel paradigm of T cell differentiation, type 17 T helper (Th17) cells may play a significant role in endometriosis, a chronic inflammatory disease. However, the mechanism regulating the accumulation of Th17 cells in endometriotic tissues remains unknown. We hypothesized that Th17 cells migrate to endometriotic tissues through an interaction of the chemokine CC chemokine ligand (CCL)20 and its receptor CCR6. Using endometriotic tissues from women with endometriosis, we demonstrated, by flo
We investigated whether Toll-like receptor (TLR) 4 is at work in the human endometrium. The expression of TLR4 mRNA in endometrial epithelial cells (EECs) and stromal cells (ESCs) was detected by RT-PCR and in situ hybridization. Western blotting analysis revealed the TLR4 protein expression in both cell populations. Treatment of lipopolysaccharide (LPS), the actions of which are mediated through TLR4, significantly increased IL-8 secretion from cultured ESCs in a dose-dependent fashion. The sti
The expression of transferrin receptors by blood monocytes, human alveolar macrophages, and in vitro matured macrophages was evaluated by immunofluorescence, radioligand binding, and Northern analysis, using the monoclonal anti-human transferrin receptor antibody OKT9, [125I]-labeled human transferrin and a [32P]-labeled human transferrin receptor cDNA probe, respectively. By immunofluorescence, the majority of alveolar macrophages expressed transferrin receptors (86 +/- 3%). The radioligand bin
Evidence-based approaches to diagnosis and treatment of extra-pelvic endometriosis remain immature given the low prevalence and limited quality of research available in the literature. To gain a better understanding of extra-pelvic endometriosis, it would be advisable to develop a registry involving a multidisciplinary collaboration with gynecologists, general surgeons, and thoracic surgeons.
The generation of induced pluripotent stem cells (iPSCs) by the forced expression of defined transcription factors in somatic cells holds great promise for the future of regenerative medicine. However, the initial reprogramming mechanism is still poorly understood. Here we show that Zscan4, expressed transiently in2-cell embryos and embryonic stem cells (ESCs), efficiently produces iPSCs from mouse embryo fibroblasts when coexpressed with Klf4, Oct4, and Sox2. Interestingly, the forced expressio
The present endometriosis model using 'green mice' would be useful for expeditious identification and quantitative evaluation of endometriotic lesions.
Adenomyosis is a common disorder in premenopausal women that causes dysmenorrhea, pelvic pain and menorrhagia. Considering that adenomyosis is an estrogen-dependent disease, the medical treatment is based on this hormone. Effective and well-tolerated medical treatments for symptomatic adenomyosis are needed. Dienogest, an oral progestin, has been extensively investigated in the treatment of endometriosis. In this report, we present the results on the efficacy and safety of dienogest in the treat
Our report suggests that dienogest is tolerable for long-term use until menopause and can be an alternative treatment option in some patients, especially those with type 2 adenomyosis, to avoid hysterectomy.
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