Innate Lymphoid Cells in Tissue Homeostasis and Disease Pathogenesis

Abstract

Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. ILCs can be categorized into three groups on the basis of the transcription factors that direct their functions and the cytokines they produce. Notably, these functions parallel the effector functions of T lymphocytes. ILCs play a frontline role in host defense and tissue homeostasis by responding rapidly to environmental factors, conducting effector responses in a tissue-specific manner, and interacting with hematopoietic and non-hematopoietic cells throughout the body. Moreover, recent studies reveal that ILCs are involved in development of various inflammatory diseases, such as respiratory diseases, autoimmune diseases, or cancer. In this review, we discuss the recent findings regarding the biology of ILCs in health and inflammatory diseases.

Keywords: development; homeostasis; inflammation; innate lymphoid cells; plasticity; tropism.

Fig. 1. Development and function of ILCs.

ILC differentiation proceeds in a stepwise fashion from hematopoietic stem cells (HSCs) to lymphoid lineage restricted precursors. The development of ILCs from CLPs requires ID2-mediated suppression of alternative lymphoid cell fates that generate B and T cells. CLPs further commit to the ILC/NK lineage via multi‐potent ILCp. Individual subsets depend on the expression of specific transcription factors that determine their terminal differentiation and function. CLP, common lymphoid progenitor; EILP, early innate lymphoid progenitor; CHILP, common helper ILC precursor; NKp, NK cell precursor; ILCp, ILC precursor; LTip, LTi cell precursor.

Fig. 2. Tissue tropism of ILCs.

ILCp derived from bone marrow hematopoiesis enters the blood to home to lymphoid and non-lymphoid organs. This process requires the expression of various chemokine receptors and α4β7 integrin. Their strategic position within tissues allows ILCs to act as a monitor of healthy tissue and to enable a rapid response to inflammatory signals. CLP, common lymphoid progenitor; ILCp, ILC precursor.

Fig. 3. Plasticity of ILCs.

ILCs exhibit plasticity that can switch between fully polarized subsets to quickly adapt to changes occurring in the environment. The plasticity of ILC1, ILC2, and ILC3 depends on signals from the tissue microenvironment, mainly the cytokine milieu.