Innate Immune System
- Study of mechanisms for the differentiation, transcriptional regulation, activation and inactivation, and cytokine response of ILC2
- Immune response of ILC2 to parasitic and fungal infections
- Pathogenesis of ILC2 in allergies, fibrosis and metabolic diseases
- Creation of therapies for ILC2-related diseases
The study of ILC2 in allergy and immune diseases
ILC2 (originally named “natural helper cells”), found in fat associated lymphoid clusters (FALC), do not express antigen-specific receptors found on many other immune cells. Nevertheless, they respond rapidly to the IL-25 and IL-33 secreted by damaged epithelial cells by secreting large amounts of IL-5 and IL-13, which leads to parasite elimination and induction of allergic responses .
The mechanism for activation of ILC2 differs from that of T helper 2 (Th2) cells, which also produce type 2 cytokines: Th2 cells do so in an antigen-specific manner, whereas ILC2 do not.
The discovery of ILC2 confirmed the existence of the ILC family, which comprises lymphocytes with helper activity in the innate system. There are now three categories of ILCs. ILC1 produce IFNγ and have antiviral and antitumor immunity. As mentioned above, ILC2 produce IL-5 and IL-13 and are associated with parasitic responses and allergies. Finally, ILC3 secrete IL-17 and IL-22 and are associated with autoimmune diseases.
Accordingly, the ILC family as a whole differ from Th cells in a number of ways. Th cells take several days to differentiate, while ILCs are present in normal tissues as mature lymphocytes. Thus, besides their role in immune responses, ILCs are believed to contribute to tissue homeostasis. ILC2, in particular, are found in tissues throughout the body including the lungs, bone, brain, muscle, skin and others. In addition to allergic reactions, they are associated with chronic inflammation in obesity and fibrosis, and play a role in rheumatoid arthritis, an autoimmune disease. Furthermore, they have been reported to interact with non-immune cells, promote the proliferation of tissue stem cells and epithelial cells for regeneration, and localize around nerves to regulate neurotransmitters.
Much of the above research has focused on mouse models, and many efforts are underway to confirm that the same properties hold true in humans. Genetic polymorphism studies have suggested ILC2-related genes such as IL-33 are associated with disease and ILC2 is being investigated as a new clinical target .
With all the above points in mind, our laboratory is conducting comprehensive analysis of ILC2, including investigation of the mechanisms for differentiation, signaling and activation and also partner cell types. The expectation is that this research will lead to new models and therapies for related immune diseases such as allergies, fibrosis, and metabolic diseases.