Model of M2d generation by LIF through an autocrine IL-6/M-CSF loop. (Top panel) In the absence of exogenous LIF or IL-6, monocytes fail to efficiently consume autocrine M-CSF and differentiate into CD86⁺IL-12⁺IL-10⁻ MΦs. (Bottom panel) Exogenous LIF induces secretion and autocrine consumption of IL-6. Exogenous LIF (pathway 1) and endogenous IL-6 (pathway 2) increase M-CSF-R turnover and facilitate M-CSF consumption, leading to ILT3⁺B7-H4⁺IL-12⁻IL-10⁺IDO⁺ M2d generation.