Lymph node-resident dendritic cells drive TH2 cell development involving MARCH1

Sci Immunol. 2021 Oct 15;6(64):eabh0707. doi: 10.1126/sciimmunol.abh0707. Epub 2021 Oct 15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Dendritic Cells / immunology*
  • Lymph Nodes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Th2 Cells / immunology*
  • Ubiquitin-Protein Ligases / deficiency
  • Ubiquitin-Protein Ligases / immunology*

Substances

  • MARCH1 protein, mouse
  • Ubiquitin-Protein Ligases