The potential role of IDO-Ahr-IL-6 axis signaling in immune regulation and stem cell proliferation

演題

The potential role of IDO-Ahr-IL-6 axis signaling in immune regulation and stem cell proliferation

講演者

Dr. Nam Trung Nguyen (Deputy Director of Institute of Biology, Head of National Key Laboratory of
Gene Technology, Vietnam Academy of Science and Technology)

使用言語

English

日時

2025年7月29日(火曜日) 13：30～14：30

場所

L12 meeting room

内容

In 2006, I got my Ph.D. from the University of Greifswald, Germany under supervision of Prof. Christine Schuett, with a thesis focused on immune regulatory mechanisms mediated by indoleamine 2,3-dioxygenase (IDO) in response to LPS stimulation. LPS is a potent inducer of pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α. My research identified IDO as a critical enzyme in the catabolism of tryptophan (Trp) into bioactive metabolites including kynurenine (KYN) which contribute to immune modulation and may serve as precursors for NAD⁺ synthesis or serotonin production. In 2007, I co-invented an WIPO patent for mechanisms regulating tryptophan metabolism through IDO. These findings have implications for new medication targeting immune tolerance, depression, and chronic fatigue syndrome (CFS).
From 2009 to 2013, during my postdoctoral and assistant professor tenure at the Immunology Frontier Research Center (IFReC), Osaka University, under supervision of Prof. Tadamitsu Kishimoto, I and other colleagues such as Dr. Taisuke Nakahama, to explore the relationship between IDO and the aryl hydrocarbon receptor (Ahr) in immune regulation. Ahr, a ligand-activated transcription factor initially studied in toxicology, has emerged as a key regulator in immune cell differentiation, particularly in T regulatory (Treg) and Th17 cell development. Our work showed that IDO and Ahr interact to modulate immune responses in macrophages, dendritic cells, and T cells. Notably, KYN and TCDD are endogenous and exogenous ligands for Ahr, respectively.
Since 2014, upon returning to Vietnam, I extended this research to populations exposed to dioxins in highly contaminated areas such as Da Nang and Bien Hoa airports. We identified a strong correlation between TCDD exposure, increased Ahr expression, elevated levels of IL-6, and a higher prevalence of autoimmune diseases such as rheumatoid arthritis. This work helped to clarify the link between environmental toxins and immune dysregulation in exposed populations. Building on this foundation, my team has screened Vietnamese medicinal plant compounds to identify natural Ahr agonists and antagonists, focusing on their regulatory effects on inflammatory cytokines through Ahr with the aim of treating the diseases in dioxin/toxic-exposed people. 
Since 2020, my research group has also paid attention to stem cell biology, investigating proliferation-enhancing strategies using cytokines, growth factors, and optimized culture conditions. We have characterized mesenchymal stem cells (MSCs) from various sources, including umbilical cords, adipose tissue, and hematopoietic tissues. Recent collaborations include projects with several hospitals, focused on cell-based therapies for cancer and type 2 diabetes. Ahr signaling has similarly been implicated in the expansion and maintenance of stem cell populations, depending on the ligand and context. A key focus of our ongoing research is the regulation of stem cell proliferation via Ahr-IDO axis (with Dr. Taisuke Nakahama, Osaka University), and bioactive peptides (with Dr. Daisuke Sugiyama, Kyushu University). 

問合せ先

Stem Cell Technogies
Kurisaki Akira (akikuri@bs.naist.jp)