Short Talk Presentation 18th International Symposium on Dendritic Cells 2026

Transcription factor Etv3 controls the tolerogenic function of dendritic cells (137732)

Nicholas M Adams 1 2 , Daniel Martinez-Krams 2 , Eduardo Esteva 2 3 , Ai C Ra 3 , Allegra Iliadi Alexiou 2 , Hua Jin 2 , Tae Jin Yun 2 , Rayan Sleiman Tellaoui 4 , Tenny Mudianto 5 , Emily Vollmer 2 , Ekaterina Novikova 2 , Yanjun Tan 2 , William Huntley 2 , Oleg Krichevsky 6 7 , Igor Dolgalev 8 9 , Peter Izmirly 9 , Jill P Buyon 9 , Andre L Moreira 2 , Amanda W Lund 2 5 , Boris Reizis 2 9 10
  1. Department of Microbiology & Immunology, University of Rochester Medical Center, Rochester, NY, USA
  2. Department of Pathology, New York University Grossman School of Medicine, New York, NY, USA
  3. Applied Bioinformatics Laboratories, New York University Grossman School of Medicine, New York, NY, USA
  4. Department of Surgery, New York University Grossman School of Medicine, New York, NY, USA
  5. Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York, NY, USA
  6. Department of Physics, Ben Gurion University of the Negev, Beer-Sheva, Israel
  7. Ilse Katz Institute for Nanoscale Science and Technology, Ben Gurion University of the Negev, Beer-Sheva, Israel
  8. Cellular Analytics Laboratory, New York University Grossman School of Medicine, New York, NY, USA
  9. Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA
  10. Department of Medicine, Section of Rheumatology and Center for Autoimmunity, University of Chicago, Chicago, IL, USA

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 CD25low regulatory T (Treg) 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 Treg 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.