Tyrosine kinase 2 is not limiting human antiviral type III interferon responses

Fuchs, Sebastian; Kaiser-Labusch, Petra; Bank, Julia; Ammann, Sandra; Kolb-Kokocinski, Anja; Edelbusch, Christine; Omran, Heymut; Ehl, Stephan

doi:10.1002/eji.201646519

Cited by 65 publications

(73 citation statements)

References 50 publications

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“…Since the last comprehensive review on MSMD in 2014, three new genetic disorders have been reported, caused by mutations of TYK2 and SPPL2A, (two novel genetic etiologies) and IFNGR2 (a novel allelic form). Moreover, new mutations associated with the other 18 disorders have also been reported . We also discuss here two recently reported syndromic forms of MSMD: AR RORγ/RORγT and Janus kinase (JAK)1 deficiencies .…”

Section: Introductionmentioning

confidence: 80%

Mendelian susceptibility to mycobacterial disease: 2014–2018 update

et al. 2018

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Mendelian susceptibility to mycobacterial disease (MSMD) is caused by inborn errors of IFN-c immunity. Since 1996, disease-causing mutations have been found in 11 genes, which, through allelic heterogeneity, underlie 21 different genetic disorders. We briefly review here progress in the study of molecular, cellular and clinical aspects of MSMD since the last comprehensive review published in 2014. Highlights include the discoveries of (1) a new genetic etiology, autosomal recessive signal peptide peptidase-like 2 A deficiency, (2) TYK2-deficient patients with a clinical phenotype of MSMD, (3) an allelic form of partial recessive IFN-cR2 deficiency, and (4) two forms of syndromic MSMD: RORc/RORcT and JAK1 deficiencies. These recent findings illustrate how genetic and immunological studies of MSMD can shed a unique light onto the mechanisms of protective immunity to mycobacteria in humans.

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Section: Introductionmentioning

confidence: 80%

Mendelian susceptibility to mycobacterial disease: 2014–2018 update

et al. 2018

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“…PGM3 deficiency is very rare and its classification as a form of HIES has not been contested [12]. Finally, TYK2 deficiency, which has been shown to underlie HIES in two families [45, 53], has been tentatively redefined as a cause of mycobacterial and viral diseases in a context of normal serum IgE levels, based on its identification in multiple families with this phenotype [11, 54]. The meaning of the term “HIES” has thus evolved considerably over the last 50 years.…”

Section: The History Of Ige and Hies In Human Diseasesmentioning

confidence: 99%

Human hyper-IgE syndrome: singular or plural?

et al. 2018

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Spectacular progress has been made in the characterization of human hyper-IgE syndrome (HIES) over the last 50 years. HIES is a primary immunodeficiency defined as an association of atopy in a context of very high serum IgE levels, characteristic bacterial and fungal diseases, low-level clinical and biological inflammation, and various non-hematopoietic developmental manifestations. Somewhat arbitrarily, three disorders were successively put forward as the underlying cause of HIES: autosomal dominant (AD) STAT3 deficiency, the only disorder corresponding to the original definition of HIES, and autosomal recessive (AR) DOCK8 and PGM3 deficiencies, in which atopy and high serum IgE levels occur in a context of manifestations not seen in patients with typical HIES. Indeed, these three disorders disrupt different molecular pathways, affect different cell types, and underlie different clinical phenotypes. Surprisingly, several other inherited inborn errors of immunity in which serum IgE levels are high, sometimes almost as high as those in HIES patients, are not considered to belong to the HIES group of diseases. Studies of HIES have been further complicated by the lack of a high serum IgE phenotype in all mouse models of the disease other than two Stat3 mutant strains. The study of infections in mutant mice has helped elucidate only some forms of HIES and infection. Mouse models of these conditions have also been used to study non-hematopoietic phenotypes for STAT3 deficiency, tissue-specific immunity for DOCK8 deficiency, and cell lineage maturation for PGM3 deficiency. We review here the history of the field of HIES since the first clinical description of this condition in 1966, together with the three disorders commonly referred to as HIES, focusing, in particular, on their mouse models. We propose the restriction of the term "HIES" to patients with an AD STAT3-deficiency phenotype, including the most recently described AR ZNF341 deficiency, thus excluding AR DOCK8 and PGM3 deficiencies from the definition of this disease.

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“…Tyrosine kinase 2 (TYK2) is an important signaling molecule to mount a functional IFN‐α response . Interestingly, type III IFN signaling and function was not influenced in a patient with TYK2‐deficiency …”

Section: Introductionmentioning

confidence: 99%

“…8 Interestingly, type III IFN signaling and function was not influenced in a patient with TYK2-deficiency. 9 Up to date, few studies investigated the physiological and immunomodulatory effect of type III IFNs, especially of IL-29, on immune cells. IL-29 appears to augment the antiviral immune response in human peripheral blood and exert different immunomodulatory effects on pDCs.…”

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confidence: 99%

Diminished secretion and function of IL-29 is associated with impaired IFN-α response of neonatal plasmacytoid dendritic cells

Wisgrill

Wessely

Netzl

et al. 2019

Journal of Leukocyte Biology

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Plasmacytoid dendritic cells (pDCs) are key players in the antiviral immune response and type III IFNs such as IL‐29 appear to play a pivotal role in pDC function. Pronounced susceptibility to viral infections in neonates is partly resulting from diminished antiviral immune mechanisms. Accordingly, the aim of the present study was to investigate the impact of IL‐29 in the altered immune response of neonatal pDCs. PBMCs of adult and term newborns were stimulated with CpG‐ODN2216 in the presence or absence of IL‐29 and assessed for IFN‐α production, downstream‐signaling, and activation marker expression. A significantly lower IL‐29 production after TLR9‐specific stimulation was demonstrated in neonatal pDCs. IL‐29 enhanced the IFN‐α production of pDCs in adults compared to newborns. Newborn pDCs displayed a significantly lower surface expression of IL‐10 and IL‐28Rα receptor resulting in diminished STAT1 and IRF7 activation. Interestingly, concomitant stimulation with CpG‐ODN2216/IL‐29 had no impact on the expression of surface activation and maturation markers of pDCs in neither population. The diminished antiviral immune response of neonatal pDCs is associated with reduced production and cellular responses toward IL‐29. Potential therapeutic agents enhancing the IL‐29 response in neonatal pDCs possibly augment viral protection in newborns.

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Tyrosine kinase 2 is not limiting human antiviral type III interferon responses

Cited by 65 publications

References 50 publications

Mendelian susceptibility to mycobacterial disease: 2014–2018 update

Mendelian susceptibility to mycobacterial disease: 2014–2018 update

Human hyper-IgE syndrome: singular or plural?

Diminished secretion and function of IL-29 is associated with impaired IFN-α response of neonatal plasmacytoid dendritic cells

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