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Interactions between fibroblastic reticular cells and B cells promote mesenteric lymph node lymphangiogenesis
Lalit Kumar Dubey1, Praneeth Karempudi1, Sanjiv A Luther2
1Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, CH-1015, Switzerland.
Nature Communications
|August 30, 2017
Summary
Lymphatic growth in lymph nodes requires lymphotoxin-beta receptor signaling between B cells and fibroblastic reticular cells. This interaction drives immune responses during helminth infection by promoting lymphatic network expansion.
Area of Science:
- Immunology
- Cell Biology
- Lymphatic System Research
Background:
- Lymphatic growth (lymphangiogenesis) within lymph nodes is crucial for immune cell trafficking during infection and inflammation.
- Understanding the cellular mechanisms driving lymph node lymphangiogenesis is essential for developing effective immune therapies.
Purpose of the Study:
- To investigate the role of lymphotoxin-beta receptor (LTβR) signaling in mesenteric lymph node lymphangiogenesis following helminth infection.
- To elucidate the cellular crosstalk between B cells and fibroblastic reticular cells (FRCs) in regulating lymphatic expansion.
Main Methods:
- Utilized a helminth infection model to study lymph node lymphangiogenesis.
- Investigated the signaling pathways involving LTβR, B-cell-activating factor (BAFF), interleukin-4 (IL-4), and vascular endothelial growth factors (VEGF-A and VEGF-C).
- Analyzed the cross-talk between B cells and FRCs.
Main Results:
- LTβR signaling to FRCs by lymphotoxin-expressing B cells is critical for mesenteric lymph node lymphangiogenesis.
- LTβR ligation on FRCs induces BAFF production, which synergizes with IL-4 to promote VEGF-A and VEGF-C production by B cells.
- This synergy also enhances lymphotoxin expression by B cells, reinforcing B cell-FRC interactions.
Conclusions:
- Lymphotoxin-dependent B cell-FRC cross-talk is fundamental for expanding lymphatic networks in mesenteric lymph nodes during helminth infection.
- This process is vital for promoting and sustaining immune responsiveness.
- The study highlights a key mechanism regulating immune cell trafficking and lymph node function.
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