Transcription factor Etv3 controls the tolerogenic function of dendritic cells
- Nicholas M. Adams
- Daniel Martinez-Krams
- Eduardo Esteva
- Ai C. Ra
- Allegra Iliadi Alexiou
- Hua Jin
- Tae Jin Yun
- Rayan Sleiman Tellaoui
- Tenny Mudianto
- Emily Vollmer
- Ekaterina Novikova
- Yanjun Tan
- William Huntley
- Oleg Krichevsky
- Igor Dolgalev
- Peter Izmirly
- Jill P. Buyon
- Andre L. Moreira
- Amanda W. Lund
- Boris Reizis
2026-02-12
Dendritic cells (DCs) facilitate the maintenance of immunological tolerance in the steady state. We report that transcription factor Etv3 is preferentially expressed in mature DCs, including tissue-derived migratory DCs (migDCs), and facilitates their homeostatic maturation and CCR7-dependent migration. Mice with global or DC-specific deletion of Etv3 manifested the expansion of CD25 low regulatory T (T reg ) cells, spontaneous activation of conventional T cells, and multiorgan T cell infiltration. Etv3 deficiency exacerbated TLR7-driven systemic lupus erythematosus (SLE)–like disease, supporting the reported genetic association of human ETV3 with SLE. Etv3-deficient migDCs up-regulated multiple costimulatory molecules, including OX40 ligand (OX40L/TNFSF4), whose blockade partially rescued the T reg cell abnormalities. These results identify Etv3 as an essential regulator of the tolerogenic function of DCs and implicate it in the regulation of human autoimmunity.