Differential Role of Cathepsins S and B In Hepatic APC-Mediated NKT Cell Activation and Cytokine Secretion

• Published in: Frontiers in immunology 2018-02, Vol.9, p.391-391
• Main Authors: de Mingo Pulido, Álvaro, de Gregorio, Estefanía, Chandra, Shilpi, Colell, Anna, Morales, Albert, Kronenberg, Mitchell, Marí, Montserrat
• Format: Article
• Language: English
• Subjects: cathepsins; Immunology; inflammation; iNKT; liver damage; NF-κB
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.00391

Natural killer T (NKT) cells exhibit a specific tissue distribution, displaying the liver the highest NKT/conventional T cell ratio. Upon antigen stimulation, NKT cells secrete Th1 cytokines, including interferon γ (IFNγ), and Th2 cytokines, including IL-4 that recruit and activate other innate immune cells to exacerbate inflammatory responses in the liver. Cysteine cathepsins control hepatic inflammation by regulating κB-dependent gene expression. However, the contribution of cysteine cathepsins other than Cathepsin S to NKT cell activation has remained largely unexplored. Here we report that cysteine cathepsins, cathepsin B (CTSB) and cathepsin S (CTSS), regulate different aspects of NKT cell activation. Inhibition of CTSB or CTSS reduced hepatic NKT cell expansion in a mouse model after LPS challenge. By contrast, only CTSS inhibition reduced IFNγ and IL-4 secretion after α-GalCer administration. Accordingly, studies reveal that only CTSS was able to control α-GalCer-dependent loading in antigen-presenting cells (APCs), probably due to altered endolysosomal protein degradation. In summary, our study discloses the participation of cysteine cathepsins, CTSB and CTSS, in the activation of NKT cells and .