The role of IL-15 as immune checkpoint
IL-15 is an apex cytokine involved in tissue homeostasis and inflammation. IL-15 is secreted by non-immune epithelial cells located at the interface with the environment, following interactions with microbes, food antigens and allergens, but also deeper into the tissues and secondary lymphoid organs by myeloid and dendritic cells. IL-15 is a key immune regulator as it orchestrates the activation and survival of many innate (NK, ILCs, MAIT cells as well as neutrophils and eosinophils) and adaptive (CD4 Th1, Th2, Th17, CD8 cytotoxic T cells as well as B cells) players. Dysregulated IL-15 expression mediates tissue inflammation and destruction through the activation of those cellular mediators. Tissue resident memory T cells perpetuate disease and have been shown to depend upon IL-15 for their survival.
Sources: Jabri & Abadie Nat.Rev.Immunol 2015; Waldmann et al. J. Exp. Med 2019; Created with BioRender
Overview of indications for CALY-002 anti-IL-15 antibody
Tissue-resident memory cells and other cells types controlled by IL-15 play an important role in the onset and maintenance of a large number of auto-immune, inflammatory and immune-metabolic diseases, some of them which are shown in the figure below.
