Research

1. Lymphangiogenesis

Lymphatic vessels serve as essential routes for the transport of antigens and antigen-presenting cells. Pathogens or external antigens that enter the body through the skin or mucosal surfaces are phagocytosed by peripheral dendritic cells or macrophages. These antigen-presenting cells then migrate through lymphatic vessels to secondary lymphoid organs, such as lymph nodes, where they present antigens to T cells and initiate adaptive immune responses.

Therefore, the regulation of lymphangiogenesis facilitates the rapid delivery of invading antigens, enhances the efficiency of antigen recognition, and promotes prompt immune responses. Recently, we have demonstrated that cytokines secreted by immune cells, including T cells, play critical roles in regulating lymphangiogenesis. Based on these findings, we are investigating strategies to enhance immune responses—such as improving vaccine efficacy—through the precise modulation of immune cells, cytokines, and lymphatic vessel formation.

2. CD4 T cell Differentiation

Helper T (Th) cells play central roles in regulating and activating diverse immune responses. These cells differentiate from a common precursor, Th0 cells, into distinct subsets such as Th1, Th2, or Th17 cells. Th1 cells primarily secrete IL-2, IFN-γ, and TNF-α, thereby promoting cell-mediated immune responses against intracellular pathogens. In contrast, Th2 cells produce cytokines, including IL-4, IL-5, IL-9, and IL-13, and are responsible for regulating immune responses against extracellular parasites. Th17 cells contribute to extracellular pathogens, such as bacteria and fungi, and produce IL-6, IL-17, and IL-22. Dysregulation of these Th subsets leads to chronic inflammatory diseases, including autoimmune and allergic disorders. 

In addition to classical antigen-presenting cell–mediated signals, we focus on the concept that stromal cells in lymph nodes and peripheral tissues provide specialized microenvironments that regulate T-cell differentiation and function. These stromal cell–derived niches influence T-cell activation, maintenance, and effector fate through local signals and cell–cell interactions. Our research aims to understand how such stromal microenvironments shape helper T-cell–mediated immune responses and contribute to chronic inflammation.

3. T cell Homing

For effector cells differentiated under specific antigenic and cytokine environments to exert their functions at the appropriate time and location, they must migrate to peripheral tissues where antigens or pathogens are present. This precise regulation of timely and site-specific cell migration represents a third critical layer of immune control and may be even more important than helper T-cell differentiation itself.

In our previous studies, we identified a cell adhesion molecule that regulates the migration of Th2 cells responsible for the development of asthma. Using gene-deficient mice, blocking antibodies, and pharmacological inhibitors, we demonstrated that selectively inhibiting Th2 cell trafficking significantly alleviates the severity of asthma. Based on these findings, our laboratory aims to elucidate the roles of factors that control Th2 cell migration and to establish their potential as therapeutic targets for asthma.

To date, Th2 cell–specific adhesion molecules that have been identified include the chemokine receptor CCR4 and the β2 integrin (CD18). Accordingly, we are developing blocking antibodies targeting these adhesion molecules and evaluating their efficacy in animal models of asthma. Through this approach, we seek to develop more fundamental immunotherapeutic strategies for asthma. Moreover, agents targeting such adhesion molecules are expected to be effective not only for asthma but also for other Th2-mediated diseases, including allergies and atopic dermatitis.