TY - JOUR
T1 - Lymph node–resident dendritic cells drive TH2 cell development involving MARCH1
AU - Castellanos, Carlos A.
AU - Ren, Xin
AU - Gonzalez, Steven Lomeli
AU - Li, Hong Kun
AU - Schroeder, Andrew W.
AU - Liang, Hong Erh
AU - Laidlaw, Brian J.
AU - Hu, Donglei
AU - Mak, Angel C.Y.
AU - Eng, Celeste
AU - Rodríguez-Santana, José R.
AU - LeNoir, Michael
AU - Yan, Qi
AU - Celedón, Juan C.
AU - Burchard, Esteban G.
AU - Zamvil, Scott S.
AU - Ishido, Satoshi
AU - Locksley, Richard M.
AU - Cyster, Jason G.
AU - Huang, Xiaozhu
AU - Shin, Jeoung Sook
N1 - Publisher Copyright:
Copyright © 2021 The Authors, some rights reserved;
PY - 2021
Y1 - 2021
N2 - Type 2 T helper (TH2) cells are protective against parasitic worm infections but also aggravate allergic inflammation. Although the role of dendritic cells (DCs) in TH2 cell differentiation is well established, the underlying mechanisms are largely unknown. Here, we show that DC induction of TH2 cells depends on membrane-associated RING-CH-1 (MARCH1) ubiquitin ligase. The pro-TH2 effect of MARCH1 relied on lymph node (LN)–resident DCs, which triggered T cell receptor (TCR) signaling and induced GATA-3 expression from naïve CD4+ T cells independent of tissue-driven migratory DCs. Mice with mutations in the ubiquitin acceptor sites of MHCII and CD86, the two substrates of MARCH1, failed to develop TH2 cells. These findings suggest that TH2 cell development depends on ubiquitin-mediated clearance of antigen-presenting and costimulatory molecules by LN-resident DCs and consequent control of TCR signaling.
AB - Type 2 T helper (TH2) cells are protective against parasitic worm infections but also aggravate allergic inflammation. Although the role of dendritic cells (DCs) in TH2 cell differentiation is well established, the underlying mechanisms are largely unknown. Here, we show that DC induction of TH2 cells depends on membrane-associated RING-CH-1 (MARCH1) ubiquitin ligase. The pro-TH2 effect of MARCH1 relied on lymph node (LN)–resident DCs, which triggered T cell receptor (TCR) signaling and induced GATA-3 expression from naïve CD4+ T cells independent of tissue-driven migratory DCs. Mice with mutations in the ubiquitin acceptor sites of MHCII and CD86, the two substrates of MARCH1, failed to develop TH2 cells. These findings suggest that TH2 cell development depends on ubiquitin-mediated clearance of antigen-presenting and costimulatory molecules by LN-resident DCs and consequent control of TCR signaling.
UR - http://www.scopus.com/inward/record.url?scp=85117926662&partnerID=8YFLogxK
U2 - 10.1126/sciimmunol.abh0707
DO - 10.1126/sciimmunol.abh0707
M3 - Article
C2 - 34652961
AN - SCOPUS:85117926662
SN - 2470-9468
VL - 6
JO - Science immunology
JF - Science immunology
IS - 64
M1 - eabh070
ER -