Altered natural killer cell cytokine profile in type 2 autoimmune hepatitis

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)31-37
Number of pages7
JournalClinical Immunology
Volume188
DOIs
Publication statusPublished - Mar 2018

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Autoimmune Hepatitis
Natural Killer Cells
Insemination, Artificial, Homologous
Cytokines
Interleukin-2
Regulatory T-Lymphocytes
KIR Receptors
Rare Diseases
Innate Immunity

Cite this

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title = "Altered natural killer cell cytokine profile in type 2 autoimmune hepatitis",
abstract = "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.",
author = "Dalila Mele and Grazia Bossi and Giuseppe Maggiore and Barbara Oliviero and Stefania Mantovani and Beatrice Bonelli and Mondelli, {Mario U} and Stefania Varchetta",
note = "Copyright {\circledC} 2017 Elsevier Inc. All rights reserved.",
year = "2018",
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language = "English",
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T1 - Altered natural killer cell cytokine profile in type 2 autoimmune hepatitis

AU - Mele, Dalila

AU - Bossi, Grazia

AU - Maggiore, Giuseppe

AU - Oliviero, Barbara

AU - Mantovani, Stefania

AU - Bonelli, Beatrice

AU - Mondelli, Mario U

AU - Varchetta, Stefania

N1 - Copyright © 2017 Elsevier Inc. All rights reserved.

PY - 2018/3

Y1 - 2018/3

N2 - 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.

AB - 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.

U2 - 10.1016/j.clim.2017.12.004

DO - 10.1016/j.clim.2017.12.004

M3 - Article

C2 - 29233784

VL - 188

SP - 31

EP - 37

JO - Clinical Immunology

JF - Clinical Immunology

SN - 1521-6616

ER -