IL-35, as a newly proposed homeostasis-associated molecular pattern, plays three major functions including anti-inflammatory initiator, effector, and blocker in cardiovascular diseases.

•IL-35 is a responsive anti-inflammatory cytokine in an antigen-independent manner.•IL-35 is an initiator anti-inflammatory cytokine by inducing Treg and Breg.•IL-35 is an effector cytokine in suppressing innate and adaptive immune responses.•IL-35 is a blocker cytokine in limiting proinflammatory cytokine signaling.•We propose that IL-35 is a novel homeostasis-associated molecular pattern (HAMP).