ZNF341 controls STAT3 expression and thereby immunocompetence

Frey-Jakobs S, Hartberger JM, Fliegauf M, Bossen C, Wehmeyer ML, Neubauer JC, Bulashevska A, Proietti M, Froebel P, Noeltner C, Yang L, Rojas-Restrepo J, Langer N, Winzer S, Engelhardt KR, Glocker C, Pfeifer D, Klein A, Schaffer AA, Lagovsky I, Lachover-Roth I, Beziat V, Puel A, Casanova JL, Fleckenstein B, Weidinger S, Kilic SS, Garty BZ, Etzioni A, Grimbacher B (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Science immunology American Association for the Advancement of Science

Book Volume: 3

Journal Issue: 24

DOI: 10.1126/sciimmunol.aat4941

Abstract

Signal transducer and activator of transcription 3 (STAT3) is a central regulator of immune homeostasis. STAT3 levels are strictly controlled, and STAT3 impairment contributes to several diseases including the monogenic autosomal-dominant hyper-immunoglobulin E (IgE) syndrome (AD-HIES). We investigated patients of four consanguineous families with an autosomal-recessive disorder resembling the phenotype of AD-HIES, with symptoms of immuno-deficiency, recurrent infections, skeletal abnormalities, and elevated IgE. Patients presented with reduced STAT3 expression and diminished T helper 17 cell numbers, in absence of STAT3 mutations. We identified two distinct homozygous nonsense mutations in ZNF341, which encodes a zinc finger transcription factor. Wild-type ZNF341 bound to and activated the STAT3 promoter, whereas the mutant variants showed impaired transcriptional activation, partly due to nuclear translocation failure. In summary, nonsense mutations in ZNF341 account for the STAT3-like phenotype in four autosomal-recessive kindreds. Thus, ZNF341 is a previously unrecognized regulator of immune homeostasis.

Authors with CRIS profile

Bernhard Fleckenstein Medizinische Fakultät

Additional Organisation(s)

Institute of Clinical and Molecular Virology

Involved external institutions

Technion - Israel Institute of Technology IL Israel (IL) Uludag University / Uludağ Üniversitesi TR Turkey (TR) Albert-Ludwigs-Universität Freiburg DE Germany (DE) Tel Aviv University IL Israel (IL) US National Institutes of Health (NIH) US United States (USA) (US) Meir Medical Center / מרכז רפואי מאיר IL Israel (IL) National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM) FR France (FR) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Newcastle University GB United Kingdom (GB)

How to cite

APA:

Frey-Jakobs, S., Hartberger, J.M., Fliegauf, M., Bossen, C., Wehmeyer, M.L., Neubauer, J.C.,... Grimbacher, B. (2018). ZNF341 controls STAT3 expression and thereby immunocompetence. Science immunology, 3(24). https://dx.doi.org/10.1126/sciimmunol.aat4941

MLA:

Frey-Jakobs, Stefanie, et al. "ZNF341 controls STAT3 expression and thereby immunocompetence." Science immunology 3.24 (2018).

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