Biology subjects

Naito, H.

Publications and source records attributed to Naito, H..

4 recordsLinked to original sources

bioRxiv2026

Modular mRNA platform for in vivo antigen-specific immune tolerance

Immune-mediated diseases such as autoimmunity and allergy arise from dysregulated antigen-specific responses, yet current therapies largely rely on broad immunosuppression and rarely re-establish durable, antigen-selective tolerance. Here we introduce Tol-mRNA, a modular tolerogenic mRNA platform designed to deliver multiple immune-regulatory signals in vivo to program antigen-specific tolerance. Tol-mRNA co-encodes an antigen together with two complementary regulatory cues, PD-L1 and TGF-{beta}, enabling coordinated antigen presentation and tolerogenic signaling that robustly induces antigen-specific Tregs and suppresses pathogenic effector responses. In murine disease models, Tol-mRNA conferred therapeutic benefit across distinct immune pathologies. In experimental autoimmune encephalomyelitis, Tol-mRNA ameliorated clinical disease and reduced inflammatory immune activation. In an ovalbumin-driven food allergy model, Tol-mRNA prevented allergic symptoms and dampened type 2 inflammation. Extending these findings to humans, Tol-mRNA demonstrated potent, antigen-dependent immunosuppressive activity and a strong capacity to promote antigen-specific Treg induction in human immune settings. Collectively, these results establish Tol-mRNA as a scalable and versatile approach to reprogram antigen-specific immunity and support its development as a next-generation therapeutic modality for immune-mediated diseases.

immunology↗

bioRxiv2025

Pathological Angiogenesis Precedes the Onset of Aortic Dissection

Aortic dissection (AD) is a severe, life-threatening disease that occurs abruptly1. Although remodeling and inherent vulnerability of the aortic media, as observed in heritable connective tissue disorders such as Marfan syndrome, have been implicated in the onset of AD, the precise pathological mechanisms underlying the non-heritable form, which accounts for most cases, remains largely unknown2. Here, using hyperacute AD patient-derived samples, we show that pathological angiogenesis within the aortic media precedes the onset of dissection. Integrating single-cell transcriptomic analysis of aortic medial endothelial cells with high-resolution imaging revealed temporal changes preceding dissection. Hypoxic alterations in the media triggered osteochondrogenic changes in smooth muscle cells, promoted hydroxyapatite deposition, and induced angiogenesis via VEGF secretion from AD-specific CD14+CD68+CD163+MRC1(CD206)neg-low macrophages. Atomic force microscopy revealed that these processes culminated in the formation of a soft capillary layer, potentially concentrating stress on this region and contributing to AD onset. H&E staining of archived specimens revealed that non-heritable AD can be classified into angiogenic or non-angiogenic subtypes, with more than half exhibiting the former. In contrast, acute AD cases associated with Marfan syndrome typically exhibit a non-angiogenic pattern, suggesting distinct underlying mechanisms. This study reports angiogenesis as a key pathological driver in non-heritable AD and highlight potential targets for early diagnosis, prevention, and treatment.

pathology↗

bioRxiv2019

A Pro-Diabetogenic mtDNA Polymorphism in the Mitochondrial-Derived Peptide, MOTS-c

Type 2 Diabetes (T2D) is an emerging public health problem in Asia. An Asian mitochondrial DNA variation m.1382A>C (rs111033358) leads to a K14Q amino acid replacement in MOTS-c, an insulin sensitizing mitochondrial-derived peptide. Meta-analysis of three cohorts (n=27,527, J-MICC, MEC, and TMM) showed that males but not females with the C-allele exhibit a higher prevalence of T2D. Furthermore, in J-MICC, only males with the C-allele in the lowest tertile of physical activity increased their prevalence of T2D, demonstrating a kinesio-genomic interaction. High-fat fed, male mice injected with MOTS-c showed reduced weight and improved glucose tolerance, but not K14Q-MOTS-c treated mice. Like the human data, female mice were unaffected. Mechanistically, K14Q-MOTS-c leads to diminished insulin-sensitization in vitro. Thus, the m.1382A>C polymorphism is associated with susceptibility to T2D in men, possibly interacting with exercise, and contributing to the risk of T2D in sedentary males by reducing the activity of MOTS-c.

genetics↗

bioRxiv2018

Mortality in trauma patients admitted during, before, and after national academic emergency medicine and trauma surgery meeting dates in Japan

Annually, many physicians attend national academic meetings. While participating in these meetings can have a positive impact on daily medical practice, attendance may result in reduced medical staffing during the meeting dates. We sought to examine whether there were differences in mortality after trauma among patients admitted to the hospital during, before, and after meeting dates. Using the Japan Trauma Data Bank, we analyzed in-hospital mortality in patients with traumatic injury admitted to the hospital from 2004 to 2015 during the dates of two national academic meetings - the Japanese Association for Acute Medicine (JAAM) and the Japanese Association for the Surgery of Trauma (JAST). We compared the data with that of patients admitted with trauma during identical weekdays in the weeks before and after the meetings, respectively. We used multiple logistic regression analysis to compare outcomes among the three groups. A total of 7,491 patients were included in our analyses, with 2,481, 2,492, and 2,518 patients in the during, before, and after meeting dates groups, respectively; their mortality rates were 7.3%, 8.0%, and 8.5%, respectively. After adjusting for covariates, no significant differences in in-hospital mortality were found among the three groups (adjusted odds ratio [95% CI] of the before meeting dates and after meeting dates groups; 1.18 [0.89-1.56] and 1.23 [0.93-1.63], respectively, with the during meeting dates group as the reference category). No significant differences in in-hospital mortality were found among trauma patients admitted during, before, and after the JAAM and JAST meeting dates.

epidemiology↗