Our laboratory focuses on answering the fundamental question of "why diseases occur" by conducting immunological analyses across a range of diseases. Among these, we are particularly interested in allergic diseases, as they have reached the status of a "national disease" in Japan, with one in two people now experiencing some form of allergy. Our goal is to deepen our understanding of the mechanisms underlying allergic responses and to use this knowledge to develop curative treatments for allergies.

In recent years, we have identified that innate lymphoid cells, a type of newly discovered lymphocyte, may play a role in establishing an "allergic predisposition" in response to changes within the body. While "predisposition" refers to a state of increased vulnerability to certain diseases, the concept has remained ambiguous and, therefore, has been challenging to study. However, if we can understand and address this "predisposition," we believe it may be possible to create a body less prone to developing allergies, effectively preventing the onset of allergic diseases.

In our lab, we are also pioneering research aimed at understanding allergic predispositions and developing methods to prevent allergies before they arise. This approach has potential applications far beyond allergic diseases alone. By examining conditions such as pulmonary fibrosis (a type of organ fibrosis), metabolic diseases like metabolic syndrome, and inflammatory bowel disease, we aim to understand and intercept the "pre-disease" state that precedes full-blown illness. We believe that identifying these early states could lead to preventive strategies for each condition.

Our ultimate goal is to contribute to a future where many diseases can be effectively prevented, paving the way for a healthier society.

Type 2 cytokines, such as IL-4, IL-5, and IL-13, trigger immune responses that protect against parasitic infections but also lead to type 2 inflammation, characterized by eosinophil infiltration, which contributes to allergic diseases. Traditionally, allergic diseases were thought to be driven primarily by T cells, but the discovery of type 2 innate lymphoid cells (ILC2s) in 2010 radically changed this understanding (Moro et al., Nature, 2010). Allergies have long been believed to be caused by allergens—substances that trigger an immune response. However, ILC2s, which are part of the innate immune system, don’t have antigen receptors like T or B cells. Instead, they are activated by various endogenous factors, including cytokines like IL-33, lipids, and neuropeptides, rather than by allergens. Once activated, ILC2s produce IL-5 and IL-13, which drive allergic reactions.

This discovery has shown that antigens are not always necessary for allergic diseases to develop, as ILC2s can respond to internal changes within the body. The identification of ILC2s has dramatically advanced our understanding of antigen-independent allergic mechanisms. For instance, conditions such as atopic dermatitis and allergic conjunctivitis, which worsen with scratching, cold-induced urticaria, and stress-exacerbated allergic diseases are examples where ILC2s play a key role. Our research (Immunity 2014, Nat. Commun 2023) has revealed that ILC2s are involved not only in allergic diseases but also in the pathogenesis of various type 2 immune disorders such as pulmonary fibrosis. To address the underlying mechanisms of these conditions, many of which remain uncured, we are focusing on elucidating the role of ILC2s in their development.