Immune modulatory therapies are widely believed to represent potential therapeutic strategies for chronic hepatitis B infection (CHB). Among the cellular targets for immune interventions, Natural Killer (NK) cells represent possible candidates because they have a key role in anti-viral control by producing cytokines and by exerting cytotoxic functions against virus-infected cells. However, in patients with chronic hepatitis B, NK cells have been described to be more pathogenic than protective with preserved cytolytic activity but with a poor capacity to produce anti-viral cytokines. In addition, NK cells can exert a regulatory activity and possibly suppress adaptive immune responses in the setting of persistent viral infections. Consequently, a potential drawback of NK-cell targeted modulatory interventions is that they can potentiate the suppressive NK cell effect on virus-specific T cells, which further causes impairment of exhausted anti-viral T cell functions. Thus, clinically useful NK-cell modulatory strategies should be not only suited to improve positive anti-viral NK cell functions but also to abrogate T cell suppression by NK cell-mediated T cell killing. This review outlines the main NK cell features with a particular focus on CHB infection. It describes different mechanisms involved in NK-T cell interplay as well as how NK cells can have positive anti-viral effector functions and negative suppressive effects on T cells activity. This review discusses how modulation of their balance can have potential therapeutic implications.
The good and the bad of natural killer cells in virus control: Perspective for anti-HBV therapy / Fisicaro, P.; Rossi, M.; Vecchi, A.; Acerbi, G.; Barili, V.; Laccabue, D.; Montali, I.; Zecca, A.; Penna, A.; Missale, G.; Ferrari, C.; Boni, C.. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 20:20(2019), p. 5080. [10.3390/ijms20205080]
The good and the bad of natural killer cells in virus control: Perspective for anti-HBV therapy
Fisicaro P.;Rossi M.;Vecchi A.;Acerbi G.;Barili V.;Montali I.;Penna A.;Missale G.;Ferrari C.Writing – Original Draft Preparation
;Boni C.
2019-01-01
Abstract
Immune modulatory therapies are widely believed to represent potential therapeutic strategies for chronic hepatitis B infection (CHB). Among the cellular targets for immune interventions, Natural Killer (NK) cells represent possible candidates because they have a key role in anti-viral control by producing cytokines and by exerting cytotoxic functions against virus-infected cells. However, in patients with chronic hepatitis B, NK cells have been described to be more pathogenic than protective with preserved cytolytic activity but with a poor capacity to produce anti-viral cytokines. In addition, NK cells can exert a regulatory activity and possibly suppress adaptive immune responses in the setting of persistent viral infections. Consequently, a potential drawback of NK-cell targeted modulatory interventions is that they can potentiate the suppressive NK cell effect on virus-specific T cells, which further causes impairment of exhausted anti-viral T cell functions. Thus, clinically useful NK-cell modulatory strategies should be not only suited to improve positive anti-viral NK cell functions but also to abrogate T cell suppression by NK cell-mediated T cell killing. This review outlines the main NK cell features with a particular focus on CHB infection. It describes different mechanisms involved in NK-T cell interplay as well as how NK cells can have positive anti-viral effector functions and negative suppressive effects on T cells activity. This review discusses how modulation of their balance can have potential therapeutic implications.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
