The MMP‐9 inhibitor has different effects with regard to the IFN‐γ to IL‐10 production and/or ratio in HC and SLE T cells because MMP‐9 inhibition in HC T cells diminishes CD46 surface shedding and the release of the CD46 ‘brake’ on Notch signaling (and hence reduces both initial IFN‐γ induction and subsequent IL‐10 switching) while MMP‐9 inhibition in SLE T cells reduces the abnormally high generation of sCD46 to levels now allowing for normal IL‐10 switching. Here, CD46 is linked to systemic lupus erythematosus.