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Published on: May 7, 2019
YAP/TAZ direct commitment and maturation of lymph node fibroblastic reticular cells
Sung Yong Choi1,2, Hosung Bae3, Sun-Hye Jeong4
1Center for Vascular Research, Institute for Basic Science (IBS), Daejeon, 34141, Republic of Korea.
Hippo signaling effectors YAP/TAZ control the development of fibroblastic reticular cells (FRCs) in lymph nodes (LNs). Dysregulation of YAP/TAZ impacts LN structure and fibrosis, offering insights into immune system organization.
Area of Science:
- Immunology
- Cell Biology
- Developmental Biology
Background:
- Fibroblastic reticular cells (FRCs) are crucial myofibroblasts in lymphoid organs, essential for lymph node (LN) structure and function.
- FRC maturation is vital for maintaining the immunological integrity and organization of LNs.
Purpose of the Study:
- To investigate the role of YAP and TAZ (YAP/TAZ), key Hippo signaling pathway components, in regulating FRC commitment and maturation.
- To elucidate the molecular mechanisms by which YAP/TAZ influence FRC development and LN homeostasis.
Main Methods:
- Utilized genetic manipulation to selectively deplete or hyperactivate YAP/TAZ in FRCs within a mouse model.
- Analyzed the impact of YAP/TAZ modulation on FRC proliferation, differentiation, LN structure, and fibrotic changes.
- Investigated molecular interactions involving YAP/TAZ, p52, and lymphotoxin-β receptor (LTβR) signaling.
Main Results:
- Selective YAP/TAZ depletion in FRCs led to impaired FRC growth, differentiation, and compromised LN structural organization.
- Hyperactivation of YAP/TAZ in FRCs resulted in enhanced myofibroblastic features and exacerbated LN fibrosis.
- Mechanistically, YAP/TAZ interaction with p52 promotes chemokine expression for FRC lineage commitment, while LTβR signaling suppresses YAP/TAZ activity during FRC maturation.
Conclusions:
- YAP/TAZ are critical regulators of both the commitment and maturation processes of fibroblastic reticular cells.
- These findings provide a deeper understanding of FRC biology and their role in LN pathophysiology.
- The study highlights YAP/TAZ as potential therapeutic targets for modulating FRC-mediated diseases.
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