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Updated: May 30, 2026
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Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
Nucleotide oligomerization domain-containing proteins instruct T cell helper type 2 immunity through stromal
Joao G Magalhaes1, Stephen J Rubino, Leonardo H Travassos
1Department of Immunology, University of Toronto, Toronto, ON, Canada M5A 2N4.
Summary
Nucleotide-binding oligomerization domain-containing proteins 1 and 2 (Nod1/Nod2) agonists initiate T-helper cell type 2 (Th2) immunity. Stromal cell Nod1/Nod2 expression is crucial for Th2 priming and antibody production, involving thymic stromal lymphopoietin and OX40 ligand.
Area of Science:
- Immunology
- Innate Immunity
- Adaptive Immunity
Background:
- Mechanisms initiating T-helper cell type 2 (Th2) immunity are not fully understood.
- Nucleotide-binding oligomerization domain-containing proteins 1 (Nod1) and 2 (Nod2) agonists are known to drive Th2 induction.
Purpose of the Study:
- To elucidate how Nod1 and Nod2 pattern-recognition receptors mediate the development of systemic Th2 immune responses.
- To identify the cellular compartments and molecules critical for Nod-mediated Th2 induction.
Main Methods:
- Utilized bone-marrow chimeric mice to investigate the role of Nod1 and Nod2 expression in different cellular compartments.
- Analyzed the contribution of dendritic cells, CD11c(+) cells, basophils, and B cells in Th2 priming.
- Assessed the involvement of thymic stromal lymphopoietin and OX40 ligand in the Th2 induction pathway.
Main Results:
- Nod1 and Nod2 expression in stromal cells is essential for priming CD4(+) Th2 responses and IgG1 antibody production.
- Dendritic cell sensing of Nod ligands alone was insufficient for Th2 immunity, though they contribute to the response.
- Thymic stromal lymphopoietin from stromal cells and OX40 ligand on dendritic cells are critical for full Th2 induction upon Nod1/Nod2 activation.
Conclusions:
- Stromal compartment expression of Nod1 and Nod2 is necessary for initiating systemic Th2 immunity.
- This study provides in vivo evidence for the mechanisms of Nod-stimulated systemic Th2 immunity.
- Findings may inform the design of therapeutics to modulate immune responses in Th1-mediated diseases like Crohn's disease.
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