Biology and therapeutic potential of human innate lymphoid cells

In the last decade, innate lymphoid cells (ILCs) have become established as important players in different areas such as tissue homeostasis, integrity of mucosal barriers and regulation of inflammation. While most of the early work on ILCs was based on murine studies, our knowledge on human ILCs is rapidly accumulating, opening novel perspectives towards the translation of ILC biology into the clinic. In this State-of-the-Art Review, we focus on the current knowledge of these most recently discovered members of the lymphocyte family and highlight their role in three major burdens of humanity: infectious diseases, cancer, and allergy and/or autoimmunity. IL-22-producing type 3 innate lymphoid cells (ILC3s) have become established as important players at the interface between gut epithelia and intestinal microbiome and are implicated in protection from inflammatory bowel disease, the control of graft-versus-host disease and intestinal graft rejection. In contrast, type 2 innate lymphoid cells (ILC2s) exert pro-inflammatory functions and contribute to the pathology of asthma and allergy, which has already been started to be pharmacologically targeted. The contribution of ILCs to the control of viral infection constitutes another emerging topic. Finally, ILCs seem to play a dual role in cancer with beneficial and detrimental contributions depending on the clinical setting. The exploitation of the therapeutic potential of ILCs will constitute an exciting task in the foreseeable future.