Keio University · Medicine
Professor Tomohisa Sujino's research lab focuses on the immunological crosstalk between the gut, skin, and microbiota, with a central emphasis on regulatory T cells (Tregs) and intraepithelial lymphocytes (IELs) in mucosal immunity. The lab investigates how environmental cues, including microbial metabolites and aryl hydrocarbon receptor (AhR) ligands, shape the development, function, and plasticity of T cells in the intestinal and skin barriers. Key research directions include the metabolic regulation of T cell differentiation, the microbiota-driven biosynthesis of immunomodulatory molecules like kynurenic acid, and the role of tissue-resident T cells in inflammatory diseases such as IBD and psoriasis. The lab also explores translational applications of natural compounds like indigo naturalis for treating colitis.
Figures are computed from collected data and may differ slightly.
Foxp3(+) regulatory T cells in peripheral tissues (pT(regs)) are instrumental in limiting inflammatory responses to nonself antigens. Within the intestine, pT(regs) are located primarily in the lamina propria, whereas intraepithelial CD4(+) T cells (CD4(IELs)), which also exhibit anti-inflammatory properties and depend on similar environmental cues, reside in the epithelium. Using intravital microscopy, we show distinct cell dynamics of intestinal T(regs) and CD4(IELs) Upon migration to the epit
These results suggest that skin inflammation may contribute to pathogenic conditions in the gut via immunologic and microbiological changes. Our finding of a novel potential skin-gut interaction provides new insights into the coincidence of psoriasis and IBD.
The intricate interplay between gut microbes and the onset of experimental autoimmune encephalomyelitis (EAE) remains poorly understood. Here, we uncover remarkable similarities between CD4<sup>+</sup> T cells in the spinal cord and their counterparts in the small intestine. Furthermore, we unveil a synergistic relationship between the microbiota, particularly enriched with the tryptophan metabolism gene EC:1.13.11.11, and intestinal cells. This symbiotic collaboration results in the biosynthesi
CD4<sup>+</sup>Foxp3<sup>+</sup> regulatory T cells (Tregs) are essential for homeostasis in the colon, but the mechanism by which local environmental cues determine the localization of colonic Tregs is unclear. Here, we administer indigo naturalis (IN), a nontoxic phytochemical aryl hydrocarbon receptor (AhR) agonist used for treating patients with ulcerative colitis (UC) in Asia, and we show that IN increases Helios<sup>+</sup> Tregs and MHC class II<sup>+</sup> epithelial cells (ECs) in the c
Intestinal intraepithelial lymphocytes (IELs), the first line of defense against microbial and dietary antigens, are classified as natural or induced based on their origin and receptor expression. Induced CD4<sup>+</sup>CD8αα<sup>+</sup>TCRβ<sup>+</sup> T cells (double positive, DP<sub>IELs</sub>) originated from CD4<sup>+</sup>CD8α<sup>-</sup>TCRβ<sup>+</sup> T cells (single positive, SP<sub>IELs</sub>) increase with aging. However, the metabolic requirements and the metabolic-related genes in
Cytotoxic CD4<sup>+</sup> T cells (CD4-CTLs) show the presence of cytolytic granules, which include the enzymes granzyme and perforin. The cells have a pathogenic and protective role in various diseases, including cancer, viral infection, and autoimmune disease. In mice, cytotoxic CD4<sup>+</sup> T cells express CD8αα<sup>+</sup> and reside in the intestine (mouse CD4<sup>+</sup>CTLs; mCD4-CTLs). The population of cytotoxic CD4<sup>+</sup> T cells in the human intestine is currently unknown. Mor
Recent studies have shown that CD4<sup>+</sup>CD8αα<sup>+</sup> T cells are induced in the hypoxic environment of the small intestinal epithelium. Herein, we describe a protocol for CD4<sup>+</sup>CD8αα<sup>+</sup> T cell induction from freshly isolated naive CD4<sup>+</sup> T cells, including procedures for the isolation and enrichment of mouse splenic T cells. In addition, we present an approach that can induce more CD4<sup>+</sup>CD8αα<sup>+</sup> T cells by artificially creating a hypoxic en
Patients with PSC showed characteristic biliary and serum BA compositions that were different from those in other groups. These findings suggest that the BA synthesis system in patients with PSC differs from that in controls and patients with other cholestatic diseases. Our approach to assessing BAs provides insights into the pathophysiology of PSC.
In this review, we summarize how Tregs are induced in the digestive tract and the application of in vivo Treg imaging to elucidate immune homeostasis in the digestive tract.
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