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Citations to this article

The NF-κB regulator MALT1 determines the encephalitogenic potential of Th17 cells
Anne Brüstle, … , Pamela S. Ohashi, Tak W. Mak
Anne Brüstle, … , Pamela S. Ohashi, Tak W. Mak
Published November 1, 2012
Citation Information: J Clin Invest. 2012;122(12):4698-4709. https://doi.org/10.1172/JCI63528.
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Research Article Immunology Article has an altmetric score of 14

The NF-κB regulator MALT1 determines the encephalitogenic potential of Th17 cells

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Abstract

Effector functions of inflammatory IL-17–producing Th (Th17) cells have been linked to autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). However, what determines Th17 cell encephalitogenicity is still unresolved. Here, we show that after EAE induction, mice deficient for the NF-κB regulator MALT1 (Malt1–/– mice) exhibit strong lymphocytic infiltration in the CNS, but do not develop any clinical signs of EAE. Loss of Malt1 interfered with expression of the Th17 effector cytokines IL-17 and GM-CSF both in vitro and in vivo. In line with their impaired GM-CSF secretion, Malt1–/– Th cells failed to recruit myeloid cells to the CNS to sustain neuroinflammation, whereas autoreactive WT Th cells successfully induced EAE in Malt1–/– hosts. In contrast, Malt1 deficiency did not affect Th1 cells. Despite their significantly decreased secretion of Th17 effector cytokines, Malt1–/– Th17 cells showed normal expression of lineage-specific transcription factors. Malt1–/– Th cells failed to cleave RelB, a suppressor of canonical NF-κB, and exhibited altered cellular localization of this protein. Our results indicate that MALT1 is a central, cell-intrinsic factor that determines the encephalitogenic potential of inflammatory Th17 cells in vivo.

Authors

Anne Brüstle, Dirk Brenner, Christiane B. Knobbe, Philipp A. Lang, Carl Virtanen, Brian M. Hershenfield, Colin Reardon, Sonja M. Lacher, Jürgen Ruland, Pamela S. Ohashi, Tak W. Mak

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 Total
Citations: 1 1 1 6 5 3 5 6 5 5 11 9 1 59
Citation information
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Citations to this article in year 2016 (5)

Title and authors Publication Year
NF-κB Pathways in the Pathogenesis of Multiple Sclerosis and the Therapeutic Implications
SM Leibowitz, J Yan
Frontiers in molecular neuroscience 2016
IKKβ-mediated inflammatory myeloid cell activation exacerbates experimental autoimmune encephalomyelitis by potentiating Th1/Th17 cell activation and compromising blood brain barrier
MJ Lee, SJ Bing, J Choi, M Jang, G Lee, H Lee, BS Chang, Y Jee, SJ Lee, IH Cho
Molecular Neurodegeneration 2016
GWAS analysis implicates NF-κB-mediated induction of inflammatory T cells in multiple sclerosis
JP Hussman, AH Beecham, M Schmidt, ER Martin, JL McCauley, JM Vance, JL Haines, MA Pericak-Vance
Genes and Immunity 2016
Alternative splicing of MALT1 controls signalling and activation of CD4+ T cells
I Meininger, RA Griesbach, D Hu, T Gehring, T Seeholzer, A Bertossi, J Kranich, A Oeckinghaus, AC Eitelhuber, U Greczmiel, A Gewies, M Schmidt-Supprian, J Ruland, T Brocker, V Heissmeyer, F Heyd, D Krappmann
Nature Communications 2016
Trim32 Deficiency Enhances Th2 Immunity and Predisposes to Features of Atopic Dermatitis
Y Liu, Z Wang, RD la Torre, A Barling, T Tsujikawa, N Hornick, J Hanifin, E Simpson, Y Wang, E Swanzey, A Wortham, H Ding, LM Coussens, M Kulesz-Martin
Journal of Investigative Dermatology 2016

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