Table 1.

Summary of IL-31 and IL-33 functions in osteoimmunology.

IL	Cytokine Family	Expression	Homeostatic Function	Receptors	Effects on Bone
IL-31	IL-6 family cytokine	Activated monocytes, myeloid progenitors, macrophages, eosinophils dendritic and CD45RO+ Th2 cells	Multiple regulatory functions on cell cycle and tissue remodeling, tissue damage and repair processes; Th2 response induction; EGF and VEGF upregulation	IL-31RA/OSMR	OPC proliferation; monocyte/macrophage activation; increased proinflammatory cytokine gene transcription, production of osteoclastogenic cytokines, matrix metalloproteinases and chemokines; Th1/Th17 lymphocyte differentiation; APC function regulation; tumorigenesis and bone metastases [29,38,102]
IL-33	IL-1 family cytokine; alarmin	Multiple organs and cell types (mainly bone marrow stromal cells, fibroblasts, epithelial and endothelial cells) following pro-inflammatory stimulation	Alerting for tissue damage; gene transcription control; immune response amplification and tissue repair during cell injury; Th2 cell maturation and chemoattraction; Th2-associated cytokine induction; eosinophil activation and mast cell degranulation; transcription of genes involved in inflammatory responses, including IL-31; Foxp3+ Treg cell induction	IL1RL1/ST2	Repression of NF-kB transcription; NFATc1 inactivation; inhibition of RANK/RANKL signaling; bone resorption decrease; OC apoptosis induction; OB function stimulation; anti-osteoclastogenic cytokine induction; maintenance of architectural bone structure in response to mechanical stimulations; OC to macrophage switch in myeloid bone marrow progenitors [29,34,108,109]

Interleukin (IL); T helper (Th); osteoclast precursor cell (OPC); osteoclast (OC); osteoblast (OB); antigen presenting cell (APC); epidermal growth factor (EGF); vascular endothelial growth factor (VEGF); T regulatory cell (Treg); nuclear factor-kB (NF-kB); nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1).