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

Sung Yong Choi; Hosung Bae; Sun-Hye Jeong; Intae Park; Hyunsoo Cho; Seon Pyo Hong; Da-Hye Lee; Choong-Kun Lee; Jin-Sung Park; Sang Heon Suh; Jeongwoon Choi; Myung Jin Yang; Jeon Yeob Jang; Lucas Onder; Jeong Hwan Moon; Han-Sin Jeong; Ralf H Adams; Jin-Man Kim; Burkhard Ludewig; Joo-Hye Song; Dae-Sik Lim; Gou Young Koh

doi:10.1038/s41467-020-14293-1

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

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

Sung Yong Choi, Hosung Bae, Sun-Hye Jeong, Intae Park, Hyunsoo Cho, Seon Pyo Hong, Da-Hye Lee, Choong-Kun Lee, Jin-Sung Park, Sang Heon Suh, …

Nature communications, Vol.11(1), pp.519-15

01/24/2020

DOI: 10.1038/s41467-020-14293-1

PMID: 31980640

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Abstract

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.

Adaptor Proteins, Signal Transducing - metabolism

Adipocytes - metabolism

Animals

Cell Cycle Proteins - metabolism

Cell Differentiation

Chemokines - metabolism

Fibroblasts - metabolism

Fibroblasts - ultrastructure

Lymph Nodes - cytology

Lymph Nodes - ultrastructure

Lymphotoxin beta Receptor - metabolism

Mesoderm - metabolism

Mice, Inbred C57BL

Myofibroblasts - metabolism

Trans-Activators - metabolism

Details

Title: Subtitle: YAP/TAZ direct commitment and maturation of lymph node fibroblastic reticular cells
Creators: Sung Yong Choi - Korea Advanced Institute of Science and Technology
Hosung Bae - Korea Advanced Institute of Science and Technology
Sun-Hye Jeong - Department of Biological Science, KAIST, Daejeon, 34141, Republic of Korea
Intae Park - Institute for Basic Science
Hyunsoo Cho - Institute for Basic Science
Seon Pyo Hong - Institute for Basic Science
Da-Hye Lee - Korea Advanced Institute of Science and Technology
Choong-Kun Lee - Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea
Jin-Sung Park - Institute for Basic Science
Sang Heon Suh - Korea Advanced Institute of Science and Technology
Jeongwoon Choi - Korea Advanced Institute of Science and Technology
Myung Jin Yang - Korea Advanced Institute of Science and Technology
Jeon Yeob Jang - Ajou University
Lucas Onder - Kantonsspital St. Gallen
Jeong Hwan Moon - Dankook University
Han-Sin Jeong - Sungkyunkwan University
Ralf H Adams - Morpho (United States)
Jin-Man Kim - Chungnam National University
Burkhard Ludewig - Kantonsspital St. Gallen
Joo-Hye Song - Institute for Basic Science
Dae-Sik Lim - Department of Biological Science, KAIST, Daejeon, 34141, Republic of Korea. daesiklim@kaist.ac.kr
Gou Young Koh - Korea Advanced Institute of Science and Technology
Resource Type: Journal article
Publication Details: Nature communications, Vol.11(1), pp.519-15
DOI: 10.1038/s41467-020-14293-1
PMID: 31980640
ISSN: 2041-1723
eISSN: 2041-1723
Language: English
Date published: 01/24/2020
Academic Unit: Internal Medicine
Record Identifier: 9985217035802771

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