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

Author

Listed:
  • Sung Yong Choi

    (Institute for Basic Science (IBS)
    Korea Advanced Institute of Science and Technology (KAIST))

  • Hosung Bae

    (KAIST)

  • Sun-Hye Jeong

    (KAIST)

  • Intae Park

    (Institute for Basic Science (IBS))

  • Hyunsoo Cho

    (Institute for Basic Science (IBS))

  • Seon Pyo Hong

    (Institute for Basic Science (IBS))

  • Da-Hye Lee

    (KAIST)

  • Choong-kun Lee

    (Institute for Basic Science (IBS)
    Korea Advanced Institute of Science and Technology (KAIST))

  • Jin-Sung Park

    (Institute for Basic Science (IBS))

  • Sang Heon Suh

    (Institute for Basic Science (IBS)
    Korea Advanced Institute of Science and Technology (KAIST))

  • Jeongwoon Choi

    (Institute for Basic Science (IBS)
    KAIST)

  • Myung Jin Yang

    (Institute for Basic Science (IBS)
    KAIST)

  • Jeon Yeob Jang

    (Ajou University School of Medicine)

  • Lucas Onder

    (Kantossipital St. Gallen)

  • Jeong Hwan Moon

    (Dankook University College of Medicine)

  • Han-Sin Jeong

    (Sungkyunkwan University School of Medicine)

  • Ralf H. Adams

    (University of Münster)

  • Jin-Man Kim

    (Chungnam National University School of Medicine)

  • Burkhard Ludewig

    (Kantossipital St. Gallen)

  • Joo-Hye Song

    (Institute for Basic Science (IBS))

  • Dae-Sik Lim

    (KAIST)

  • Gou Young Koh

    (Institute for Basic Science (IBS)
    Korea Advanced Institute of Science and Technology (KAIST)
    KAIST)

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.

Suggested Citation

  • 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 , 2020. "YAP/TAZ direct commitment and maturation of lymph node fibroblastic reticular cells," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14293-1
    DOI: 10.1038/s41467-020-14293-1
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