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 |
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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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