Background: Interleukin (IL)-37 is a potent anti-inflammatory cytokine of the IL-1 family that can broadly suppress inflammation and immunity. Extracellularly, IL-37 signals via formation of a functional complex with the receptor proteins IL-1R8 and IL-1R5 on the cell surface to initiate its anti-inflammatory signaling cascade. However, the expression and regulation of the IL-37 receptor (IL-37R) and its effect on the intracellular mechanism of action of IL-37 are not fully understood.
Methods: Here we characterised IL-37R expression in peripheral leukocyte subsets such as lymphocytes, monocytes, and dendritic cells in human whole blood from healthy donors and patients with inflammatory conditions including systemic lupus erythematosus, rheumatoid arthritis, and respiratory, neurological, and gastrointestinal disease. We also investigated the stimuli that induce IL-37R and the response of IL-37R+ cells to extracellular recombinant IL-37 stimulation.
Results: We show that T cells are the major contributor to the total IL-37R+ population in healthy adult whole blood and that monocytes and dendritic cells are highly inducible for IL-37R. We also observed differences in IL-37R expression between health and disease contexts which has implications for assessing donor-specific responses to IL-37.
Conclusion: IL-37 is a strategic target for drug development because of its ability to broadly suppress inflammation. Our study identifies the effector cells expressing IL-37R and their regulation and provides information for specific drug-target interaction studies.