Transcription factor Etv3 controls the tolerogenic function of dendritic cells.
basic_science · Level V
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- Record sourced from PubMed, PMID 41678619.
- Also identified by DOI 10.1126/science.ads1246 and PMC identifier 12977282.
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Abstract
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<sup>low</sup> regulatory T (T<sub>reg</sub>) 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 <i>ETV3</i> with SLE. Etv3-deficient migDCs up-regulated multiple costimulatory molecules, including OX40 ligand (OX40L/TNFSF4), whose blockade partially rescued the T<sub>reg</sub> 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.
Medical subject headings
- Dendritic Cells
- DNA-Binding Proteins
- Immune Tolerance
- Lupus Erythematosus, Systemic
- Proto-Oncogene Proteins c-ets
- Transcription Factors
- Repressor Proteins