Innate lymphoid cells in tissue homeostasis and diseases

Abstract

Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. They are a part of the innate immune system, but develop from the lymphoid lineage. They lack pattern-recognition receptors and rearranged receptors, and therefore cannot directly mediate antigen specific responses. The progenitors specifically associated with the ILCs lineage have been uncovered, enabling the distinction between ILCs and natural killer cells. Based on the requirement of specific transcription factors and their patterns of cytokine production, ILCs are categorized into three subsets (ILC1, ILC2 and ILC3). First observed in mucosal surfaces, these cell populations interact with hematopoietic and non-hematopoietic cells throughout the body during homeostasis and diseases, promoting immunity, commensal microbiota tolerance, tissue repair and inflammation. Over the last 8 years, ILCs came into the spotlight as an essential cell type able to integrate diverse host immune responses. Recently, it became known that ILC subsets play a key role in immune responses at barrier surfaces, interacting with the microbiota, nutrients and metabolites. Since the liver receives the venous blood directly from the intestinal vein, the intestine and liver are essential to maintain tolerance and can rapidly respond to infections or tissue damage. Therefore, in this review, we discuss recent findings regarding ILC functions in homeostasis and disease, with a focus on the intestine and liver.

Keywords: Innate lymphoid cells; Intestine; Liver; Homeostasis; Inflammatory diseases

Core tip: Receiving approximately 70% of blood through the portal vein, the liver represents one of the most important sites of defense against invading pathogens. In addition, the liver and the intestine are important immune organs, as they are often in contact with antigens and endotoxins produced by the gut microbiota. These organs are densely populated by innate immune cells such as natural killer cells, dendritic cells, macrophages, natural killer T cells and innate lymphoid cells (ILCs), which are rapidly activated by commensal and pathogenic antigens, growth factors, cytokines and host metabolites. Recent studies have been focused on discovering the role of ILCs and how these cell populations can regulate the immune response. Our goal is to discuss innovative literature highlighting the importance of ILCs in the context of infectious disease, tissue repair, tolerance of gut microbiota and inflammatory diseases that affect the liver and intestine homeostasis.