About this Research Topic

Background

Innate Lymphoid Cells (ILCs) belong to a heterogeneous group of developmentally related lymphocytes that have been classified into four different groups mirroring by function and transcriptional regulation respective T cells counterparts. In particular, ILC1, ILC2, and ILC3 functions reflect those of CD4+ T helper (Th) cells (Th1, Th2 and Th17, respectively), while Natural Killer (NK) cells mirror CD8+ cytotoxic T cells subset.

ILCs are involved in host defenses against pathogens and tumors, in lymphoid organogenesis, and in maintenance of tissue homeostasis i.e. remodeling and repair upon injury. Their functions are strongly affected by the microenvironment and thus, changes in microenvironmental conditions can shift the balance of their responses toward either productive or pathological. As several studies have demonstrated their involvement in driving the various inflammatory diseases, tissue injury and carcinogenesis, their potential in immunotherapy is currently exploited.

ILCs’ ability to discriminate between healthy and stressed (infected or transformed) cells is finely regulated by an array of receptors that deliver either activating and inhibitory signals, or information from the surrounding microenvironment. These include not only cytokine receptors that receive information about inflammatory status in the tissue, but also the receptors that sense tissue injury via “alarmins”, and the receptors that integrate data about chemical and physical properties of the cell surrounding, such as nutrient, metabolite or oxygen concentration. A plethora of ILC sensors is able to interact with ligands specifically induced or up-regulated by damaged cells, whose activation is counterbalanced by inhibitory signals. Important inhibitory checkpoints, such as PD-1, TIM-3, TIGIT, or LAG-3, play a pivotal role in regulating the overall immune responses and maintain immune cell homeostasis in physiological conditions. In the context of tumor, the development of immune checkpoint inhibitors (ICI) in order to enforce T cell activation, has represented an innovative and efficient immunotherapeutic approach that is widely used to treat several cancer types. The knowledge of their importance in controlling ILC functions, and eventually their exhaustion and impairment, as described for T cells, is emerging. Similarly, the overall impact of other sensors that locally in the microenvironment can diminish or increase ILC functions demands further systematic understanding. Apart from anti-tumor immunity, where “classical” checkpoints play significant roles, ILC checkpoints in other inflammatory conditions, such as infection or autoimmunity require additional consideration.

Accordingly, in this Research Topic we welcome Original Papers and Reviews on checkpoints expression, function and regulation in ILC cells that cover some of the following subjects:

1) Role of checkpoints in both pathological and physiological conditions

2) Molecular mechanisms controlling checkpoint expression and their function

3) Pathway activated by checkpoint receptors, and their regulation

4) Immunotherapeutic approaches targeting ILC cells checkpoints

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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