Versatile roles of innate lymphoid cells at the mucosal barrier: from homeostasis to pathological inflammation

Innate lymphoid cells (ILCs) are innate lymphocytes that do not express antigen-specific receptors and largely reside and self-renew in mucosal tissues. ILCs can be categorized into three groups (ILC1–3) based on the transcription factors that direct their functions and the cytokines they produce. Their signature transcription factors and cytokines closely mirror those of their Th1, Th2, and Th17 cell counterparts. Accumulating studies show that ILCs are involved in not only the pathogenesis of mucosal tissue diseases, especially respiratory diseases, and colitis, but also the resolution of such diseases. Here, we discuss recent advances regarding our understanding of the biology of ILCs in mucosal tissue health and disease. In addition, we describe the current research on the immune checkpoints by which other cells regulate ILC activities: for example, checkpoint molecules are potential new targets for therapies that aim to control ILCs in mucosal diseases. In addition, we review approved and clinically- trialed drugs and drugs in clinical trials that can target ILCs and therefore have therapeutic potential in ILC-mediated diseases. Finally, since ILCs also play important roles in mucosal tissue homeostasis, we explore the hitherto sparse research on cell therapy with regulatory ILCs. This review highlights various therapeutic approaches that could be used to treat ILC-mediated mucosal diseases and areas of research that could benefit from further investigation. Immunology: the role of innate lymphoid cells Cells of the immune system called innate lymphoid cells (ILCs) patrol the soft ‘mucosal’ tissues lining the respiratory, digestive and reproductive organs, where they can be involved in both the recovery from and development of disease. Researchers in South Korea led by Hye Young Kim at Seoul National University, review recent advances in understanding the biology of ILCs in mucosal tissue health and disease. ILCs are part of the innate immune system, which elicits immediate and general responses to infection and disease, rather than responses to specific foreign substances. The authors discuss physiological mechanisms that regulate ILCs, which could be targeted for future drug development. They also review the potential of existing drugs that could target ILCs to treat disease, especially inflammatory conditions, and the possible use of ILCs as cell-based therapies for various diseases.