Yoko Hamazaki

Claudins, most of which end in valine at their COOH termini, constitute tight junction (TJ) strands, suggesting that TJ strands strongly attract PDZ-containing proteins. Indeed, ZO-1, -2, and -3, each of which contains three PDZ domains, were shown to directly bind to claudins. Using the yeast two-hybrid system, we identified ZO-1 and MUPP1 (multi-PDZ domain protein 1) as binding partners for the COOH terminus of claudin-1. MUPP1 has been identified as a protein that contains 13 PDZ domains, but

Whether age-associated defects in T cells impact the immunogenicity and reactogenicity of mRNA vaccines remains unclear. Using a vaccinated cohort (n = 216), we demonstrated that older adults (aged ≥65 years) had fewer vaccine-induced spike-specific CD4⁺ T cells including CXCR3⁺ circulating follicular helper T cells and the T_H1 subset of helper T cells after the first dose, which correlated with their lower peak IgG levels and fewer systemic adverse effects after

Claudin (Cld)-4 is one of the dominant Clds expressed in the kidney and urinary tract, including selective segments of renal nephrons and the entire urothelium from the pelvis to the bladder. We generated Cldn4(-/-) mice and found that these mice had increased mortality due to hydronephrosis of relatively late onset. While the renal nephrons of Cldn4(-/-) mice showed a concomitant diminution of Cld8 expression at tight junction (TJ), accumulation of Cld3 at TJ was markedly enhanced in compensati

The thymus consists of two distinct anatomical regions, the cortex and the medulla; medullary thymic epithelial cells (mTECs) play a crucial role in establishing central T-cell tolerance for self-antigens. Although the understanding of mTEC development in thymic organogenesis as well as the regulation of their differentiation and maturation has improved, the mechanisms of postnatal maintenance remain poorly understood. This issue has a central importance in immune homeostasis and physiological t

Enteroendocrine cells are solitary epithelial cells scattered throughout the gastrointestinal tract and produce various types of hormones, constituting one of the largest endocrine systems in the body. The study of these rare epithelial cells has been hampered by the difficulty in isolating them because of the lack of specific cell surface markers. Here, we report that enteroendocrine cells selectively express a tight junction membrane protein, claudin-4 (Cld4), and are efficiently isolated with

Hassall's corpuscles (HCs) are composed of cornifying, terminally differentiated medullary thymic epithelial cells (mTECs) that are developed under the control of Aire. Here, we demonstrated that HC-mTECs show features of cellular senescence and produce inflammatory cytokines and chemokines including CXCL5, thereby recruiting and activating neutrophils to produce IL-23 in the thymic medulla. We further indicated that thymic plasmacytoid dendritic cells (pDCs) expressing IL-23 receptors constitut

The thymus is the primary lymphoid organ for generating self-restricted and self-tolerant functional T cells. Its two distinct anatomical regions, the cortex and the medulla, are involved in positive and negative selection, respectively. Thymic epithelial cells (TECs) constitute the framework of this tissue and function as major stromal components. Extensive studies for more than a decade have revealed how TECs are generated during organogenesis; progenitors specific for medullary TECs (mTECs) a

Naïve phenotype (NP) T cells spontaneously initiate homeostatic proliferation (HP) as T-cell output is reduced because of physiologic thymic involution with age. However, the effects of sustained HP on overall immune function are poorly understood. We demonstrated that the NP CD8⁺ T cell population in adult thymectomized mice showing accelerated HP has an increased capacity for TCR-mediated interferon-γ and tumor necrosis factor α production, which is attributed to an increase in CXCR

T-cell development depends on the thymic microenvironment, in which endothelial cells (ECs) play a vital role. Interestingly, vascular permeability of the thymic cortex is lower than in other organs, suggesting the existence of a blood-thymus barrier (BTB). On the other hand, blood-borne molecules and dendritic cells bearing self-antigens are accessible to the medulla, facilitating central tolerance induction, and continuous T-precursor immigration and mature thymocyte egress occur through the v

Age is a major risk factor for COVID-19 severity, and T cells play a central role in anti-SARS-CoV-2 immunity. Because SARS-CoV-2-cross-reactive T cells have been detected in unexposed individuals, we investigated the age-related differences in pre-existing SARS-CoV-2-reactive T cells. SARS-CoV-2-reactive CD4⁺ T cells from young and elderly individuals were mainly detected in the central memory fraction and exhibited similar functionalities and numbers. Naïve-phenotype SARS-CoV-2-reac

Age-associated differences in the effect of repetitive vaccination, particularly on memory T-cell and B-cell responses, remain unclear. While older adults (aged ≥65 years) exhibited enhanced IgG responses following COVID-19 mRNA booster vaccination, they produced fewer spike-specific circulating follicular helper T cells-1 than younger adults. Similarly, the cytotoxic CD8⁺ T-cell response remained diminished with reduced PD-1 expression even after booster vaccination compared with tha