Beyond Antagonism: IL-4 Exploits TNF signaling to Shape Its Gene Expression Signature in Monocytes and Macrophages.

ABSTRACT: Investigation of crosstalk between antagonistic pro- and anti-inflammatory cytokines has focused on mechanisms and functional consequences of cross-inhibition. We investigated cross-regulation between proinflammatory TNF and anti-inflammatory IL-4 in primary human monocytes and in a skin wound-healing model. Surprisingly, TNF functioned mainly as a costimulator of IL-4-induced gene expression, whereas IL-4 selectively inhibited the TNF-induced IFN response, leaving inflammatory gene expression mostly intact. TNF and IL-4 synergistically induced gene sets important for regulating inflammation and tissue repair, which were highly induced during the phase of wound healing when these cytokines are co-expressed. Crosstalk between TNF and IL-4 was mediated by epigenetic chromatin-mediated mechan

SUBMITTER: Yuan R 

PROVIDER: S-EPMC12324305 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature