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Coordination of YAP/TAZ Activity and Lymphotoxin-β Receptor Signaling Governs Maturation and Integrity of Fibroblastic Reticular Cells in Lymph Nodes

64 Pages Posted: 26 Feb 2019 Publication Status: Review Complete

See all articles by Sung Yong Choi

Sung Yong Choi

Institute for Basic Science (IBS) - Center for Vascular Research

Hosung Bae

Institute for Basic Science (IBS) - Center for Vascular Research

Sun-Hye Jeong

Korea Advanced Institute of Science and Technology (KAIST) - Department of Biological Sciences

Intae Park

Institute for Basic Science (IBS) - Center for Vascular Research

Choong-kun Lee

Institute for Basic Science (IBS) - Center for Vascular Research

Jin-Sung Park

Institute for Basic Science (IBS) - Center for Vascular Research

Sang Heon Suh

Institute for Basic Science (IBS) - Center for Vascular Research

Jeongwoon Choi

Institute for Basic Science (IBS) - Center for Vascular Research

Jeon Yeob Jang

Ajou University - Department of Otorhinolaryngology

Lucas Onder

Kantonsspital St. Gallen - Institute of Immunobiology

Jeong Hwan Moon

Dankook University - Department of Otorhinolaryngology - Head and Neck Surgery

Han-Sin Jeong

Sungkyunkwan University - Department of Otorhinolaryngology - Head and Neck Surgery

Ralf H. Adams

University of Muenster - Faculty of Medicine

Jin-Man Kim

Chungnam National University - Department of Pathology

Burkhard Ludewig

Kantonsspital St. Gallen - Institute of Immunobiology

Joo-Hye Song

Institute for Basic Science (IBS) - Center for Vascular Research

Dae-Sik Lim

Korea Advanced Institute of Science and Technology (KAIST) - Department of Biological Sciences

Gou Young Koh

Korea Advanced Institute of Science and Technology (KAIST) - Graduate School of Medical Science and Engineering

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Abstract

Fibroblastic reticular cells (FRCs) serve as a scaffolding microarchitecture for lymph nodes (LNs) and respond dynamically to various stimuli. However, the regulatory signaling pathways that govern the structural and functional adaptations of FRCs are poorly understood. Here, we show that YAP and TAZ, the end effectors of Hippo signaling, are dominant regulators of maturation and maintenance of FRCs. Constant or inducible genetic deletion or hyperactivation of YAP/TAZ led to impaired differentiation and maintenance of FRCs to varying degrees, leading to disrupted formation and compartmentalization of LNs and their immune responsiveness. Activation of LTβR signaling facilitated binding of p52 to YAP/TAZ and suppressed their transcriptional activities. Intriguingly, double deletion of YAP/TAZ and LTβR signaling transformed FRCs into adipocytes. Thus, LTβR signaling acts as a regulator of YAP/TAZ in FRCs. Accordingly, reduced LTβR signaling in the LNs harboring metastatic tumor promoted YAP/TAZ activity, leading to LN fibrosis and reduced anti-cancer immunity.

Suggested Citation

Choi, Sung Yong and Bae, Hosung and Jeong, Sun-Hye and Park, Intae and Lee, Choong-kun and Park, Jin-Sung and Suh, Sang Heon and Choi, Jeongwoon and Jang, Jeon Yeob and Onder, Lucas and Moon, Jeong Hwan and Jeong, Han-Sin and Adams, Ralf H. and Kim, Jin-Man and Ludewig, Burkhard and Song, Joo-Hye and Lim, Dae-Sik and Koh, Gou Young, Coordination of YAP/TAZ Activity and Lymphotoxin-β Receptor Signaling Governs Maturation and Integrity of Fibroblastic Reticular Cells in Lymph Nodes (September 26, 2018). Available at SSRN: https://ssrn.com/abstract=3255565 or http://dx.doi.org/10.2139/ssrn.3255565
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Sung Yong Choi

Institute for Basic Science (IBS) - Center for Vascular Research

55, Expo-ro, Yuseong-gu
Daejeon, 34126
Korea, Republic of (South Korea)

Hosung Bae

Institute for Basic Science (IBS) - Center for Vascular Research

55, Expo-ro, Yuseong-gu
Daejeon, 34126
Korea, Republic of (South Korea)

Sun-Hye Jeong

Korea Advanced Institute of Science and Technology (KAIST) - Department of Biological Sciences

Daejeon, 34141
Korea, Republic of (South Korea)

Intae Park

Institute for Basic Science (IBS) - Center for Vascular Research

55, Expo-ro, Yuseong-gu
Daejeon, 34126
Korea, Republic of (South Korea)

Choong-kun Lee

Institute for Basic Science (IBS) - Center for Vascular Research

55, Expo-ro, Yuseong-gu
Daejeon, 34126
Korea, Republic of (South Korea)

Jin-Sung Park

Institute for Basic Science (IBS) - Center for Vascular Research

55, Expo-ro, Yuseong-gu
Daejeon, 34126
Korea, Republic of (South Korea)

Sang Heon Suh

Institute for Basic Science (IBS) - Center for Vascular Research

55, Expo-ro, Yuseong-gu
Daejeon, 34126
Korea, Republic of (South Korea)

Jeongwoon Choi

Institute for Basic Science (IBS) - Center for Vascular Research

55, Expo-ro, Yuseong-gu
Daejeon, 34126
Korea, Republic of (South Korea)

Jeon Yeob Jang

Ajou University - Department of Otorhinolaryngology

Woncheon-dong, Yeongtong-gu
Suwon-si, Gyeonggi-do
Korea, Republic of (South Korea)

Lucas Onder

Kantonsspital St. Gallen - Institute of Immunobiology

Rorschacher Str. 95
St. Gallen, 9007
Switzerland

Jeong Hwan Moon

Dankook University - Department of Otorhinolaryngology - Head and Neck Surgery

126, Jukjeon-dong, Suji-gu, Yo
Gyeonggi-do
Korea, Republic of (South Korea)

Han-Sin Jeong

Sungkyunkwan University - Department of Otorhinolaryngology - Head and Neck Surgery

81, Irwon- Ro
Gangnam-gu
Seoul, 135-710
Korea, Republic of (South Korea)

Ralf H. Adams

University of Muenster - Faculty of Medicine

Schlossplatz 2
Muenster, D-48149
Germany

Jin-Man Kim

Chungnam National University - Department of Pathology

Daejon, 35015
Korea, Republic of (South Korea)

Burkhard Ludewig

Kantonsspital St. Gallen - Institute of Immunobiology ( email )

Rorschacher Str. 95
St. Gallen, 9007
Switzerland

Joo-Hye Song

Institute for Basic Science (IBS) - Center for Vascular Research

55, Expo-ro, Yuseong-gu
Daejeon, 34126
Korea, Republic of (South Korea)

Dae-Sik Lim

Korea Advanced Institute of Science and Technology (KAIST) - Department of Biological Sciences

Daejeon, 34141
Korea, Republic of (South Korea)

Gou Young Koh (Contact Author)

Korea Advanced Institute of Science and Technology (KAIST) - Graduate School of Medical Science and Engineering ( email )

291 Daehak-ro, Yuseong-gu
Daejeon, 305-701
Korea, Republic of (South Korea)

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