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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, 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

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.
citation Choi S Y, Bae H, Jeong S H, Park I, Cho H, Hong S P, Lee D H, Lee C K, Park J S, Suh S H, Choi J, Yang M J, Jang J Y, Onder L, Moon J H, Jeong H S, Adams R H, Kim J M, Ludewig B, Song J H, Lim D S, Koh G Y. YAP/TAZ direct commitment and maturation of lymph node fibroblastic reticular cells. Nat Commun 2020; 11:519.
type journal paper/review (English)
date of publishing 24-01-2020
journal title Nat Commun (11/1)
ISSN electronic 2041-1723
pages 519
PubMed 31980640
DOI 10.1038/s41467-020-14293-1