Altered natural killer cell cytokine profile in type 2 autoimmune hepatitis

Publication date: Available online 9 December 2017
Source:Clinical Immunology
Author(s): Dalila Mele, Grazia Bossi, Giuseppe Maggiore, Barbara Oliviero, Stefania Mantovani, Beatrice Bonelli, Mario U. Mondelli, Stefania Varchetta
Type 2 autoimmune hepatitis (AIH-2) is a rare disease presenting in early childhood. The immunopathogenetic mechanisms are poorly characterized, although a defect of regulatory T cells (Treg) has been shown. There is virtually no information on innate immune responses and natural killer (NK) cells in particular. We have performed an extended immunophenotypic and functional analysis of NK cells in children with AIH-2. We show that NK cell frequency is reduced in this setting and that the balance between NK activating and inhibitory receptors is skewed toward activation. More importantly, NK cells display an altered cytokine pattern characterized by increased IFNγ and reduced IL2 production which could contribute to impaired Treg function. Exposure of mononuclear cells to IL2 resulted in normalization of NK IFNγ production. Thus, our findings support treatment of AIH-2 with low-dose IL2, which would result in normalization of NK cell function and expansion of the Treg cell subset.

Graphical abstract

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