Alternative splicing controls cell lineage-specific responses to endogenous innate immune triggers within the extracellular matrix

•Pro-inflammatory signals from the matrix drive innate immune responses.•Both activated stromal and immune cells produce one such trigger, tenascin-C.•Different cell lineages exhibit very distinct modes of tenascin-C biosynthesis.•Isoforms lacking domains AD2AD1 are up-regulated in activated and diseased cells.•AD2AD1 suppresses immune cell chemotaxis and TLR4-dependent cytokine release.