Journal Article

ISG15 modulates inflammatory profiles and ability to activate CD8 + T cells in bone marrow-derived dendritic cells

Castillo-González, Raquel, Fernández-Delgado, Irene, Moya-Ruiz, Elena, Martín-Gayo, Enrique, Martínez-Fleta, Pedro, Ramírez-Huesca, Marta, Sánchez-Madrid, Francisco, Guerra, Susana, Pertusa, Clara, Izquierdo-Serrano, Raúl, Fernández-Gallego, Nieves, Calzada-Fraile, Diego

2025

Overview

The Interferon-Stimulated Gene 15 (ISG15) has a key role during viral infections, since it can modify and regulate the expression of proteins from the host and from viruses. Isg15 −/− mice are more susceptible to infectious diseases. ISG15 is induced by type I Interferons (IFN-I) and apart from defense against pathogens, it can also play an important function in cancer or immune-mediated inflammatory diseases. Previous studies reported that ISG15 expression is increased in post-synaptic dendritic cells (DCs) upon interaction with CD4 + T cells. However, data regarding the role of ISG15 in DCs are scarce. The present study assesses the function of ISG15 in DCs activation, migration and ability to mediate T cell activation using bone marrow-derived DCs (BMDCs) and stimulation with lipopolysaccharide (LPS). Activation of DCs was not impaired but tended to be lower in Isg15 -deficient mice, as observed by reduced CD40 induction in Isg15 −/− BMDCs. Isg15 −/− BMDCs induced less proliferation and Granzyme B expression in co-cultured CD8 + T cells. Interestingly, Isg15 −/− BMDCs secreted reduced levels of the pro-inflammatory cytokines IL-1β and IL-12 upon LPS stimulation. Mechanistically, our data suggest that ISG15 regulates Caspase-1 activity in DCs leading to lower IL-1 β secretion. In conclusion, this study reveals an essential role for ISG15 modulating DCs inflammatory activity and raises new questions regarding the specific mechanisms of how this protein regulates innate immune responses.

• Publisher: Springer International Publishing,Springer Nature B.V,Springer
• Subject: Animals / Antigens / Biochemistry / Biomedical and Life Sciences / Biomedicine / Bone marrow / Bone Marrow Cells - cytology / Bone Marrow Cells - immunology / Caspase-1 / CD4 antigen / CD40 antigen / CD8 antigen / CD8-Positive T-Lymphocytes - cytology / CD8-Positive T-Lymphocytes - immunology / CD8-Positive T-Lymphocytes - metabolism / Cell activation / Cell Biology / Cell Movement / Cell Proliferation / Cells, Cultured / Cytokines / Cytokines - genetics / Cytokines - metabolism / Dendritic cells / Dendritic Cells - cytology / Dendritic Cells - immunology / Dendritic Cells - metabolism / Enzymes / Flow cytometry / Genes / Granzyme B / IL-1β / Immune response / Infectious diseases / Inflammasome / Inflammation - immunology / Inflammation - metabolism / Inflammation - pathology / Inflammatory diseases / Innate immunity / Interferon / Interleukins / ISG15 / Life Sciences / Lipopolysaccharides / Lipopolysaccharides - pharmacology / Lymphocyte Activation / Lymphocytes / Lymphocytes T / Mice / Mice, Inbred C57BL / Mice, Knockout / Original Article / Pathogens / Proteins / Stains & staining / Stimulation / Transgenic animals / Tumor necrosis factor-TNF / Ubiquitins - genetics / Ubiquitins - metabolism / Viral infections