Uterus transplantation (UTx) is now a potential option to allow women with uterine factor infertility to give birth. However, UTx is still at an experimental stage, and basic animal studies, including in non-human primates, are needed for the accumulation of data prior to clinical application. Considering that UTx may provide new hope to Japanese women, we launched UTx research in 2009 and have since accumulated a large archive of results in the UTx research field. Furthermore, we have carried out various activities aimed at the implementation of clinical applications of UTx in Japan while clarifying the ethical and social issues involved. Currently, the clinical application of UTx in Japan is just around the corner, and it is expected that UTx research will develop further in the future. Herein, we summarize our basic experiences using non-human primates and our activities with the goal of future clinical applications.

Many operative procedures have been reported for the management of chronic lateral ankle instability, and anatomical reconstructions are an excellent option. However, if the remnants of the ligaments are considerably damaged, anatomical reconstructions using such remnants can be difficult. In cases such as these, tenodesis stabilization may be required. However, tenodesis stabilization often restricts the range of ankle movement. The purpose of this study was to determine the effectiveness of a new procedure that we developed to mitigate the problems associated with tenodesis stabilization procedures. We installed grafts in the original anatomical position by devising a system for positioning the drill holes in the bones so that our procedure did not restrict the range of ankle movement. A retrospective review of 37 patients (13 men, 24 women) with a mean age of 30.2 (range, 16–66) years was performed at an average of 69 (range, 47–77) months after the surgery. The average American Orthopaedic Foot and Ankle Society ankle–hindfoot score improved significantly from 65.6 (range, 47–77) points preoperatively to 98.0 (range, 87–100) points postoperatively (P < 0.001). With the number of subjects available, no significant differences were detected between the postoperative mean ranges of movement of the ankle and subtalar joints and those of the preoperative ankle. Patients who underwent anatomical tenodesis reconstructions with a free split peroneal brevis tendon showed good outcomes after a 69-month follow-up period.

Infection with Yersinia pseudotuberculosis, a known causal pathogen of human bacterial gastroenteritis, causes various symptoms and complications. A previously healthy 7-year-old girl was admitted because of fever and gastrointestinal symptoms. She was initially diagnosed with intussusception by abdominal ultrasonography. Although the patient was successfully treated by air enema, the fever persisted. The patient was then diagnosed with incomplete Kawasaki disease based on the presence of four principal clinical features. Intravenous immunoglobulin and oral aspirin were initiated. The patient defervesced and the other symptoms subsided after the treatment. Cardiac ultrasound results showed normal coronary arteries. Because of the gastrointestinal symptoms, stool samples were cultured repeatedly, only to yield normal flora. However, serum levels of anti-Y. pseudotuberculosis-derived mitogen antibody were elevated between the 7th and 18th days of the disease, thereby confirming Y. pseudotuberculosis infection. Because Y. pseudotuberculosis infection results in various clinical manifestations, we must be aware of each symptom and address them systematically.

The skin is not merely a physical barrier but also an active immunological interface, exposed to various external stimuli including microbes. Over the recent years, our laboratory has defined hair follicles as control towers that regulates immune cells residing in the skin. Hair follicles produce chemokines and cytokines that are crucial for the localization and tissue-residency of immune cells including the Langerhans cells, resident memory T cells, and innate lymphoid cells. We also discovered that disruption of the ADAM17-EGF receptor axis and ADAM10-Notch signaling axis leads to dysbiosis on the skin surface and in the hair follicles, respectively. The former leads to microbiome predominance of Staphylococcus aureus and results in atopic skin inflammation, whereas the latter leads to Corynebacterium species predominance that trigger irreversible hair follicle destruction. These findings highlight the distinct mechanisms that regulate the microbiome in different compartments of the skin. In this talk, I will focus on the deeper layers of the skin-the hypodermis (a.k.a subcutaneous tissue), a common site for cellulitis, which we found to be enriched with macrophages. We enabled layer-specific depletion of macrophages, which had prominent effects on the organization of the extracellular matrix, counterintuitively rendering mice highly protected against S. aureus-mediated cellulitis. I will also introduce our ongoing efforts to understand the histology and pathophysiology of Degos disease, an extremely rare and highly fatal disease of unknown etiology.