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

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.

Nat Commun. 2020 Jan 24;11(1):519

Authors: Choi SY, Bae H, Jeong SH, Park I, Cho H, Hong SP, Lee DH, Lee CK, Park JS, Suh SH, Choi J, Yang MJ, Jang JY, Onder L, Moon JH, Jeong HS, Adams RH, Kim JM, Ludewig B, Song JH, Lim DS, Koh GY

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.

PMID: 31980640 [PubMed - in process]