MAFB and MAF cooperatively orchestrate human anti-inflammatory macrophage identity via autocrine Interleukin-10

In human M-CSF-dependent monocyte-derived macrophages, MAFB and MAF form a stable heterodimer on chromatin, with MAFB acting as the primary global anchor of anti-inflammatory identity.

• Why it matters: The field lacks a clear, non-redundant map of how MAFB and MAF coordinate to control human anti-inflammatory macrophage programs and their functional plasticity.
• What they did: Using integrated proteomic, transcriptomic, and epigenomic profiling plus CUT&Tag, the study shows both factors bind the IL10 locus, while IL-10 expression is primarily driven by MAFB. Neutralizing antibody assays test the role of endogenous IL-10 in macrophage identity.
• The result: Endogenously produced IL-10 creates an obligate autocrine feedback loop required for both initial acquisition and maintenance of the anti-inflammatory profile, with MAFB and MAF separately tuning efferocytosis/T cell activation and phagocytosis/pro-inflammatory cytokine hyper-induction.

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