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 () and Gou Young Koh ()
Additional contact information
Sung Yong Choi: Institute for Basic Science (IBS)
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)
Jin-Sung Park: Institute for Basic Science (IBS)
Sang Heon Suh: Institute for Basic Science (IBS)
Jeongwoon Choi: Institute for Basic Science (IBS)
Myung Jin Yang: Institute for Basic Science (IBS)
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)

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-14293-1

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