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 V. Novikova, Yanjun Tan, William Huntley, Oleg Krichevsky, Igor Dolgalev, Peter Izmirly, Jill P. Buyon, André L. Moreira, Amanda W. Lund, Boris Reizis
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.