Publications by authors named "Laureen A Gabriel"

2 Publications

  • Page 1 of 1

Balanced Bcl-3 expression in murine CD4 T cells is required for generation of encephalitogenic Th17 cells.

Eur J Immunol 2017 08 29;47(8):1335-1341. Epub 2017 Jun 29.

Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

The function of NF-κB family members is controlled by multiple mechanisms including the transcriptional regulator Bcl-3, an atypical member of the IκB family. By using a murine model of conditional Bcl-3 overexpression specifically in T cells, we observed impairment in the development of Th2, Th1, and Th17 cells. High expression of Bcl-3 promoted CD4 T-cell survival, but at the same time suppressed proliferation in response to TCR stimulation, resulting in reduced CD4 T-cell expansion. As a consequence, T-cell-specific overexpression of Bcl-3 led to reduced inflammation in the small intestine of mice applied with anti-CD3 in a model of gut inflammation. Moreover, impaired Th17-cell development resulted in the resistance of Bcl-3 overexpressing mice to EAE, a mouse model of multiple sclerosis. Thus, we concluded that fine-tuning expression of Bcl-3 is needed for proper CD4 T-cell development and is required to sustain Th17-cell mediated pathology.
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http://dx.doi.org/10.1002/eji.201746933DOI Listing
August 2017

IL-1 signaling is critical for expansion but not generation of autoreactive GM-CSF+ Th17 cells.

EMBO J 2017 01 8;36(1):102-115. Epub 2016 Nov 8.

Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

Interleukin-1 (IL-1) is implicated in numerous pathologies, including multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). However, the exact mechanism by which IL-1 is involved in the generation of pathogenic T cells and in disease development remains largely unknown. We found that following EAE induction, pertussis toxin administration leads to IL-1 receptor type 1 (IL-1R1)-dependent IL-1β expression by myeloid cells in the draining lymph nodes. This myeloid-derived IL-1β did not vitally contribute to the generation and plasticity of Th17 cells, but rather promoted the expansion of a GM-CSF Th17 cell subset, thereby enhancing its encephalitogenic potential. Lack of expansion of GM-CSF-producing Th17 cells led to ameliorated disease in mice deficient for IL-1R1 specifically in T cells. Importantly, pathogenicity of IL-1R1-deficient T cells was fully restored by IL-23 polarization and expansion in vitro Therefore, our data demonstrate that IL-1 functions as a mitogenic mediator of encephalitogenic Th17 cells rather than qualitative inducer of their generation.
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http://dx.doi.org/10.15252/embj.201694615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210124PMC
January 2017