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Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
Published on: September 26, 2013
The NF-κB transcription factor c-Rel is required for Th17 effector cell development in experimental autoimmune
Guobing Chen1, Kristine Hardy, Eloisa Pagler
1Gene Expression and Epigenomics Laboratory, Department of Genome Biology, The John Curtin School of Medical Research, Australian National University, Canberra 2600, Australia.
Journal of Immunology (Baltimore, Md. : 1950)
|September 24, 2011
Summary
Mice lacking c-Rel show impaired development of Th17 cells, a key driver of experimental autoimmune encephalomyelitis (EAE). This c-Rel deficiency impacts EAE severity through altered Th17 and regulatory T cell balance.
Area of Science:
- Immunology
- Molecular Biology
- Autoimmune Diseases
Background:
- Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune disease.
- Effector T helper (Th) cell subsets, including Th1 and Th17, are critical in EAE pathogenesis.
- The transcription factor c-Rel's role in EAE and Th17 development is not fully understood.
Purpose of the Study:
- To investigate the role of the NF-κB transcription factor c-Rel in the development of Th17 cells and its impact on EAE.
- To elucidate the mechanisms by which c-Rel regulates Th17 differentiation and influences EAE severity.
Main Methods:
- Utilized mice lacking the c-Rel gene (rel(-/-)) and wild-type littermates.
- Employed mixed bone marrow chimeras and adoptive transfer experiments in EAE models.
- Analyzed T cell receptor (TCR) signaling, gene expression (Rorc), and regulatory T cell differentiation.
Main Results:
- Mice lacking c-Rel exhibited impaired Th17 cell development, a T cell-intrinsic defect.
- c-Rel activation was crucial for Th17 differentiation by controlling Rorc expression.
- c-Rel modulated Th17 development influenced by CD28 signaling and affected regulatory T cell homeostasis.
Conclusions:
- c-Rel plays a multifaceted role in regulating EAE development and severity.
- c-Rel is essential for Th17 cell generation and influences the balance between Th17 and regulatory T cells.
- These findings highlight c-Rel as a key regulator in autoimmune T cell responses.
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