YAP/TAZ direct commitment and maturation of lymph node fibroblastic reticular cells

Autor: Joo Hye Song, Jeong Hwan Moon, Sun-Hye Jeong, Lucas Onder, Jeon Yeob Jang, Hyunsoo Cho, Burkhard Ludewig, Seon Pyo Hong, Intae Park, Dae-Sik Lim, Jeongwoon Choi, Sung Yong Choi, Sang Heon Suh, Ralf H. Adams, Gou Young Koh, Da-Hye Lee, Jin-Sung Park, Jin-Man Kim, Myung Jin Yang, Han-Sin Jeong, Choong-kun Lee, Hosung Bae
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Chemokine
Science
Cellular differentiation
Organogenesis
General Physics and Astronomy
Cell Cycle Proteins
General Biochemistry
Genetics and Molecular Biology
Article
Mesoderm
03 medical and health sciences
0302 clinical medicine
Reticular cell
Lymphotoxin beta Receptor
Developmental biology
medicine
Adipocytes
Animals
lcsh:Science
Myofibroblasts
Lymph node
Adaptor Proteins
Signal Transducing
Lymphokines
Multidisciplinary
biology
Signal transducing adaptor protein
Cell Differentiation
YAP-Signaling Proteins
General Chemistry
respiratory system
Fibroblasts
Cell biology
respiratory tract diseases
Mice
Inbred C57BL
030104 developmental biology
Lymphatic system
medicine.anatomical_structure
Hippo signaling
030220 oncology & carcinogenesis
biology.protein
Trans-Activators
lcsh:Q
Lymph Nodes
Chemokines
Myofibroblast
circulatory and respiratory physiology
Zdroj: Nature Communications
Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020)
ISSN: 2041-1723
Popis: Fibroblastic reticular cells (FRCs) are immunologically specialized myofibroblasts of lymphoid organ, and FRC maturation is essential for structural and functional properties of lymph nodes (LNs). Here we show that YAP and TAZ (YAP/TAZ), the final effectors of Hippo signaling, regulate FRC commitment and maturation. Selective depletion of YAP/TAZ in FRCs impairs FRC growth and differentiation and compromises the structural organization of LNs, whereas hyperactivation of YAP/TAZ enhances myofibroblastic characteristics of FRCs and aggravates LN fibrosis. Mechanistically, the interaction between YAP/TAZ and p52 promotes chemokine expression that is required for commitment of FRC lineage prior to lymphotoxin-β receptor (LTβR) engagement, whereas LTβR activation suppresses YAP/TAZ activity for FRC maturation. Our findings thus present YAP/TAZ as critical regulators of commitment and maturation of FRCs, and hold promise for better understanding of FRC-mediated pathophysiologic processes.
Fibroblastic reticular cells (FRC) are important for lymph node (LN) structure and function. Here the authors show that the YAP/TAZ complex downstream of Hippo signalling regulates FRC commitment and maturation, with YAP/TAZ deficiency impairing FRC differentiation, while hyperactivation of YAZ/TAZ inducing myofibroblastic FRCs and LN fibrosis.
Databáze: OpenAIRE
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