TY  - JOUR
A1  - Eberhardt, Christiane S.
A1  - Haas, Johannes-Peter
A1  - Girschick, Hermann
A1  - Schwarz, Tobias
A1  - Morbach, Henner
A1  - Rösen-Wolff, Angela
A1  - Foell, Dirk
A1  - Dannecker, Guenther
A1  - Schepp, Carsten
A1  - Ganser, Gerd
A1  - Honke, Nora
A1  - Eggermann, Thomas
A1  - Müller-Berghaus, Jan
A1  - Wagner, Norbert
A1  - Ohl, Kim
A1  - Tenbrock, Klaus
T1  - No association of IL-12p40 pro1.1 polymorphism with juvenile idiopathic arthritis
JF  - Pediatric Rheumatology
N2  - Background: IL-12p40 plays an important role in the activation of the T-cell lines like Th17 and Th1-cells. Theses cells are crucial in the pathogenesis of juvenile idiopathic arthritis. A polymorphism in its promoter region and the genotype IL12p40 pro1.1 leads to a higher production of IL-12p40. We studied whether there is a difference in the distribution of the genotype in patients with JIA and the healthy population. 
Methods: In 883 patients and 321 healthy controls the IL-12p40 promoter genotype was identified by ARMS-PCR. 
Results: There is no association of IL-12p40 pro polymorphism neither in patients with JIA compared to controls nor in subtypes of JIA compared to oligoarthritis. We found a non-significant tendency of a higher prevalence of the genotype pro1.1 in systemic arthritis (32.4 %) and in rheumatoid factor negative polyarthritis (30.5 %) and a lower pro1.1 genotype in persistent oligoarthritis (20.7 %) and in enthesitis-related arthritis (17 %). Likelihood of the occurrence of genotype IL12-p40 pro1.1 in patients with systemic arthritis (OR 1.722, CI 95 % 1.344-2.615, p 0.0129) and RF-negative polyarthritis (OR 1.576, CI 95 % 1.046-2.376, p 0.0367) compared to persistent oligoarthritis was significantly higher. This was also true for comparison of their homozygous genotypes IL-12p40 pro 1.1 and 2.2 in systemic arthritis (OR 1.779, CI 95 % 1.045-3.029, p 0.0338). However, in Bonferroni correction for multiple hypothesis this was not significant. 
Conclusion: A tendency of a higher prevalence of the genotype IL-12p40 pro1.1 in systemic arthritis and in rheumatoid factor negative polyarthritis was observed but not significant. Further investigations should be done to clarify the role IL-12p40 in the different subtypes of JIA.
KW  - polymorphism
KW  - cytokine
KW  - children
KW  - serum
KW  - IL12B
KW  - gene
KW  - cells
KW  - juvenile idiopathic arthritis
KW  - IL-12p40
KW  - IL-12B
KW  - promoter
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-136281
VL  - 13
IS  - 61
ER  - 
TY  - JOUR
A1  - Luu, Maik
A1  - Riester, Zeno
A1  - Baldrich, Adrian
A1  - Reichardt, Nicole
A1  - Yuille, Samantha
A1  - Busetti, Alessandro
A1  - Klein, Matthias
A1  - Wempe, Anne
A1  - Leister, Hanna
A1  - Raifer, Hartmann
A1  - Picard, Felix
A1  - Muhammad, Khalid
A1  - Ohl, Kim
A1  - Romero, Rossana
A1  - Fischer, Florence
A1  - Bauer, Christian A.
A1  - Huber, Magdalena
A1  - Gress, Thomas M.
A1  - Lauth, Matthias
A1  - Danhof, Sophia
A1  - Bopp, Tobias
A1  - Nerreter, Thomas
A1  - Mulder, Imke E.
A1  - Steinhoff, Ulrich
A1  - Hudecek, Michael
A1  - Visekruna, Alexander
T1  - Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer
JF  - Nature Communications
N2  - Emerging data demonstrate that the activity of immune cells can be modulated by microbial molecules. Here, we show that the short-chain fatty acids (SCFAs) pentanoate and butyrate enhance the anti-tumor activity of cytotoxic T lymphocytes (CTLs) and chimeric antigen receptor (CAR) T cells through metabolic and epigenetic reprograming. We show that in vitro treatment of CTLs and CAR T cells with pentanoate and butyrate increases the function of mTOR as a central cellular metabolic sensor, and inhibits class I histone deacetylase activity. This reprogramming results in elevated production of effector molecules such as CD25, IFN-γ and TNF-α, and significantly enhances the anti-tumor activity of antigen-specific CTLs and ROR1-targeting CAR T cells in syngeneic murine melanoma and pancreatic cancer models. Our data shed light onto microbial molecules that may be used for enhancing cellular anti-tumor immunity. Collectively, we identify pentanoate and butyrate as two SCFAs with therapeutic utility in the context of cellular cancer immunotherapy.
KW  - tumour immunology
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-309332
VL  - 12
ER  -