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Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice
Published on: March 24, 2017
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Splenic Architecture and Function Requires Tight Control of Transmembrane TNF Expression
Kim C M Jeucken1,2, Merlijn H Kaaij1,2, Jasper Rip3,4
1Department of Experimental Immunology, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
International Journal of Molecular Sciences
|February 26, 2022
Summary
Transmembrane tumor necrosis factor (tmTNF) overexpression alters secondary lymphoid organ development. Aberrant tmTNF signaling impacts spleen and lymph node structure and function, highlighting its critical role in immune regulation.
Area of Science:
- Immunology
- Cell Biology
- Developmental Biology
Background:
- Soluble tumor necrosis factor (sTNF) is a key inflammatory mediator crucial for immune organ development.
- The role of transmembrane tumor necrosis factor (tmTNF) in secondary lymphoid organ (SLO) development and function is less understood.
Purpose of the Study:
- To investigate the impact of tmTNF overexpression on SLO architecture and function.
- To elucidate the signaling pathways involved in tmTNF-mediated effects on SLOs.
Main Methods:
- Utilized tmTNF-transgenic (tmTNF-tg) mice to study tmTNF overexpression.
- Analyzed spleen and peripheral lymph node (PLN) morphology, cellular composition, and immune cell populations.
- Investigated the role of TNF receptor I (TNFRI) and TNF receptor II (TNFRII) by genetic deletion.
Main Results:
- tmTNF overexpression led to enlarged PLNs and spleen with altered lymphoid follicle structure.
- Reduced germinal center (GC) B cells, T follicular helper (Tfh) cells, and T follicular regulatory (Tfr) cells were observed in the spleen.
- Plasma cell formation decreased and skewed towards IgA and IgM in tmTNF-tg mice spleens.
- Genetic deletion of TNFRI/II partially normalized follicle morphology but not GC B cell or plasma cell abnormalities.
Conclusions:
- Tightly regulated tmTNF is essential for proper SLO development and function.
- Aberrations in tmTNF signaling cause site-specific defects in SLOs, mediated via TNFRI and/or TNFRII.
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