Systemic sterile induced-co-expression of IL-12 and IL-18 drives IFN--dependent activation of microglia and recruitment of MHC-II-expressing myeloid cells to the brain.

GAVIGLIO EMILIA; PERALTA-RAMOS JAVIER; ARROYO DANIELA; BUSSI CLAUDIO ; IRIBARREN PABLO; RODRIGUEZ GALÁN, MARÍA CECILIA

INTERNATIONAL IMMUNOPHARMACOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2022 vol. 105

1567-5769

he development of neuroinflammation, as well as the progression of several neurodegenerative diseases, has been associated with the activation and mobilization of the peripheral immune system due to systemic inflammation. However, the mechanism by which this occurs remains unclear. Here, we addressed the effect of systemic sterile induced-co-expression of IL-12 and IL-18, in the establishment of a novel cytokine-mediated model of neuroinflammation. Following peripheral hydrodynamic shear of IL-12 plus IL-18 cDNAs in C57BL/6 mice, we induced systemic and persistent level of IL-12, which in turn promoted the elevation of circulating proinflammatorycytokines TNF-α and IFN-γ, accompanied with splenomegaly. Moreover, even though we identifiedan increased gene expression of both TNF-α and IFN-γ in the brain, we observed that only IFN-γ, but not TNF-α signaling through its type I receptor, was required to induce both the trafficking of leukocytes from the periph