TY  - JOUR
A1  - Ballin, Nadja
A1  - Hotz, Alrun
A1  - Bourrat, Emmanuelle
A1  - Küsel, Julia
A1  - Oji, Vinzenz
A1  - Bouadjar, Bakar
A1  - Brognoli, Davide
A1  - Hickman, Geoffroy
A1  - Heinz, Lisa
A1  - Vabres, Pierre
A1  - Marrakchi, Slaheddine
A1  - Leclerc‐Mercier, Stéphanie
A1  - Irvine, Alan
A1  - Tadini, Gianluca
A1  - Hamm, Henning
A1  - Has, Cristina
A1  - Blume‐Peytavi, Ulrike
A1  - Mitter, Diana
A1  - Reitenbach, Marina
A1  - Hausser, Ingrid
A1  - Zimmer, Andreas D.
A1  - Alter, Svenja
A1  - Fischer, Judith
T1  - Genetical, clinical, and functional analysis of a large international cohort of patients with autosomal recessive congenital ichthyosis due to mutations in NIPAL4
JF  - Human Mutation
N2  - Autosomal recessive congenital ichthyosis (ARCI) belongs to a heterogeneous group of disorders of keratinization. To date, 10 genes have been identified to be causative for ARCI. NIPAL4 (Nipa‐Like Domain‐Containing 4) is the second most commonly mutated gene in ARCI. In this study, we present a large cohort of 101 families affected with ARCI carrying mutations in NIPAL4. We identified 16 novel mutations and increase the total number of pathogenic mutations in NIPAL4 to 34. Ultrastructural analysis of biopsies from six patients showed morphological abnormalities consistent with an ARCI EM type III. One patient with a homozygous splice site mutation, which leads to a loss of NIPAL4 mRNA, showed additional ultrastructural aberrations together with a more severe clinical phenotype. Our study gives insights into the frequency of mutations, a potential hot spot for mutations, and genotype–phenotype correlations.
KW  - ARCI
KW  - ARCI EM type III
KW  - collodion baby
KW  - ichthyosis
KW  - NIPAL4
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212747
VL  - 40
IS  - 12
ER  - 
TY  - JOUR
A1  - Rolvering, Catherine
A1  - Zimmer, Andreas D.
A1  - Ginolhac, Aurélien
A1  - Margue, Christiane
A1  - Kirchmeyer, Mélanie
A1  - Servais, Florence
A1  - Hermanns, Heike M.
A1  - Hergovits, Sabine
A1  - Nazarov, Petr V.
A1  - Nicot, Nathalie
A1  - Kreis, Stephanie
A1  - Haan, Serge
A1  - Behrmann, Iris
A1  - Haan, Claude
T1  - The PD-L1-and IL6-mediated dampening of the IL27/STAT1 anticancer responses are prevented by alpha-PD-L1 or alpha-IL6 antibodies
JF  - Journal of Leukocyte Biology
N2  - Interleukin-27 (IL27) is a type-I cytokine of the IL6/IL12 family and is predominantly secreted by activated macrophages and dendritic cells. We show that IL27 induces STAT factor phosphorylation in cancerous cell lines of different tissue origin. IL27 leads to STAT1 phosphorylation and recapitulates an IFN--like response in the microarray analyses, with up-regulation of genes involved in antiviral defense, antigen presentation, and immune suppression. Like IFN-, IL27 leads to an up-regulation of TAP2 and MHC-I proteins, which mediate increased tumor immune clearance. However, both cytokines also upregulate proteins such as PD-L1 (CD274) and IDO-1, which are associated with immune escape of cancer. Interestingly, differential expression of these genes was observed within the different cell lines and when comparing IL27 to IFN-. In coculture experiments of hepatocellular carcinoma (HCC) cells with peripheral blood mononuclear cells, pre-treatment of the HCC cells with IL27 resulted in lowered IL2 production by anti-CD3/-CD28 activated T-lymphocytes. Addition of anti-PD-L1 antibody, however, restored IL2 secretion. The levels of other T(H)1 cytokines were also enhanced or restored upon administration of anti-PD-L1. In addition, we show that the suppression of IL27 signaling by IL6-type cytokine pre-stimulationmimicking a situation occurring, for example, in IL6-secreting tumors or in tumor inflammation-induced cachexiacan be antagonized by antibodies against IL6-type cytokines or their receptors. Therapeutically, the antitumor effects of IL27 (mediated, e.g., by increased antigen presentation) might thus be increased by combining IL27 with blocking antibodies against PD-L1 or/and IL6-type cytokines.
KW  - cytokine
KW  - interferon
KW  - IFN-gamma
KW  - IDO-1
KW  - OSM
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226974
VL  - 104
IS  - 5
ER  -