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Hanna Niehues, PhD, Berenice Rösler, MSc, Danique A

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1 STAT1 gain-of-function compromises skin host defense in the context of IFN-γ signaling 
Hanna Niehues, PhD, Berenice Rösler, MSc, Danique A. van der Krieken, MSc, Ivonne M.J.J. van Vlijmen-Willems, BSc, Diana Rodijk- Olthuis, BSc, Malou Peppelman, PhD, Joost Schalkwijk, PhD, Ellen H.J. van den Bogaard, PhD, Patrick L.J.M. Zeeuwen, PhD, Frank L. van de Veerdonk, MD, PhD  Journal of Allergy and Clinical Immunology  Volume 143, Issue 4, Pages e5 (April 2019) DOI: /j.jaci Copyright © Terms and Conditions

2 Fig 1 Aberrant morphology and protein expression of STAT1 GOF HEEs on IFN-γ stimulation. H&E and IHC stainings of wild-type and STAT1 GOF (A) untreated or (B) IFN-γ–treated HEEs. N = 3 patient keratinocyte donors and N = 5 donors of normal keratinocytes. Black arrowheads highlight the most evident differences in morphology and protein expression of STAT1 GOF HEEs. Scale bar = 100 μm. H&E, Hematoxylin and eosin; K10, keratin 10. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © Terms and Conditions

3 Fig 2 Antifungal LCE3 proteins expressed at different anatomical locations. A, Mean CFU/mL C albicans of N = 2 replicates after 2 hours of incubation in the presence of synthetic LCE3 protein. B, H&E (upper panel) and immunohistochemical staining of LCE3 protein (lower panel) at different anatomical sites: trunk (N = 10), foot (N = 2), hand (N = 6), and gingiva (N = 5). Scale bar = 100 μm. H&E, Hematoxylin and eosin. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © Terms and Conditions

4 Fig E1 Wild-type and STAT1 GOF HEEs stimulated with TH17 cytokines. HEEs were stimulated with (A) 50 ng/mL IL-17 or (B) 50 ng/mL IL-22, respectively, during the last 72 hours of air-liquid interface culture. Photographs show H&E as well as immunohistochemical stainings for Ki67, K10, LOR, SKALP/elafin, and LCE3 protein. Scale bar = 100 μm. N = 2. H&E, Hematoxylin and eosin; K10, keratin 10. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © Terms and Conditions

5 Fig E2 Wild-type and STAT3 LOF HEEs stimulated with IFN-γ. H&E and LCE3 protein stainings of wild-type and STAT3 loss-of-function untreated or IFN-γ–treated HEEs. N = 2 patient keratinocyte donors and N = 2 donors of normal keratinocytes. H&E, Hematoxylin and eosin; LOF, loss-of-function. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © Terms and Conditions

6 Fig E3 Schematic drawing of STAT1 GOF skin defects and C albicans infection. After an inflammatory insult, caused by external stimuli, disturbed epidermal differentiation and loss of LCE3 protein is seen at specific locations of STAT1 GOF skin. This results in aberrant skin barrier function and increased susceptibility to C albicans colonization and infection. Journal of Allergy and Clinical Immunology  , e5DOI: ( /j.jaci ) Copyright © Terms and Conditions

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