Table 2.

Functions, regulation, and mechanisms of IL-37.

Function, regulation, or mechanism	Reference
Suppresses innate immunity and inflammation	[3]
Suppresses adaptive immunity	[20]
Upregulated after stimulation of LPS, Pam3CSK4, and TGF-β1	[3]
Induced by IL-1β, TNF, IFN-γ, IL-18, TGF-β, and TLR ligands	[3]
Suppressed by GM-CSF combined with IL-4	[3]
Suppresses proinflammatory cytokines: IL-1α, IL-1β, IL-1Ra, IL-6, IL-8, IL-17, IL-23, TNF-α, and IFN-γ	[3, 8]
Suppresses chemokines: MIP-2/CXCL2, CCL12/MCP-5, and BCA-1/CXCL13	[3, 8]
Inhibits M-GSF and GM-CSF	[3, 8]
Increases the immunosuppressive factor TGF-β1	[3, 8]
Induces the expression of nitric oxide in vitro	[16]
Inhibits DCs functions	[20]
Attenuates T cell-mediated inflammation	[20]
Interacts with Smad3	[3]
Inhibits the STATs, p38MAPK, ERK1/2, JNK, FAK, Pyk2, paxillin, NF-κB, kinase Fyn, TAK1	[3, 8, 12, 28–30]
Inhibits NLRP3 inflammasome	[3, 16]
Binds to IL-18Rα to form a complex with IL-18BP, thereby reduces the activity of IL-18	[9, 16, 33, 36]
Binds to SIGIRR	[12, 16, 38]
Protective factor in mouse model of LPS-induced shock	[3]
Limits tissue injury during infections	[3, 16]
Potential protective factor in ischemia-reperfusion injury	[44, 49, 50]
Potential protective role in autoimmune diseases	[5, 6]
Potential antitumor effect	[7, 13, 21, 23–25]
Potential protective factor in cardiovascular diseases	[81, 84]
Related to obesity and insulin resistance	[88, 89]

TLR: Toll-like receptor. LPS: lipopolysaccharide. FAK: focal adhesion kinase. Pyk2: proline-rich tyrosine kinase 2; NLRP3: NOD-like receptor family Pyrin Domain-Containing 3. SIGIRR: single immunoglobulin IL-1 receptor related protein.