Lymph node-resident dendritic cells drive T_H2 cell development involving MARCH1

Type 2 T helper (T_H2) cells are protective against parasitic worm infections but also aggravate allergic inflammation. Although the role of dendritic cells (DCs) in T_H2 cell differentiation is well established, the underlying mechanisms are largely unknown. Here, we show that DC induction of T_H2 cells depends on membrane-associated RING-CH-1 (MARCH1) ubiquitin ligase. The pro-T_H2 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 T_H2 cells. These findings suggest that T_H2 cell development depends on ubiquitin-mediated clearance of antigen-presenting and costimulatory molecules by LN-resident DCs and consequent control of TCR signaling.