Regulatory Role of ILC2 in Acute Lung Injury in Sepsis

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Severe sepsis complicated with multiple organ dysfunction syndrome (MODS) is a leading cause of death in ICU. Acute lung injury (ALI) is an important component of MODS and often serves as a direct cause of death. Nonetheless, few effective therapeutic targets for ALI have been identified. Our long-term goal is to determine the mechanisms by which sepsis promote ALI, thereby potentially identifying novel targets for prophylactic intervention. Innate lymphoid cells (ILCs), a new member of the lymphoid population, play a central role in innate immunity of host response to inflammation, infection, and tissue damage. ILCs are composed of three subgroups, ILC1, ILC2, and ILC3. ILC2 are a main ILC subtype in the lungs in both human and mouse, and play an important role in maintaining airway barrier integrity and lung tissue homeostasis. However, the role of ILC2 in sepsis-induced ALI remains unclear. This research project aims to understand the regulatory role of ILC2 in the development and progression of ALI and the mechanism underlying ILC2 mobilization, migration, and expansion in the lung in sepsis through three Specific Aims (SA): SA1. To determine the role of ILC2 in the progression of ALI following sepsis; SA2 To determine the mechanism underlying ILC2 mobilization from BM and migration into the lung in sepsis; and SA3 To determine the mechanism of ILC2 expansion in the lung in sepsis. The results of the study will serve as essential foundation for potential novel treatment of ALI in sepsis by regulating ILC2 migration, expansion, and function.