Fig. 5

Proposed hypothetic model of NETosis as a non-canonical release mechanism of ISG15. In lupus patients, the NETs cargo is consistent with augmented amount of ISG15, which colocalized with H2B and induce the polarization of CD4, CD8 and NK to a Th1 subset that enhanced the production of IFNγ through LFA1 (CD11a/β1 integrin) (a). Low concentrations of ISG15 were found in healthy controls NETs with a diminished colocalization with H2B and reduction of Th1 IFNγ + CD4, CD8 and NK cells (b). Therefore, we proposed that ISG15 is a fingerprint of the interferogenic signature, and its release is mediated through NETosis in lupus patients