Genome-Wide Screening Identifies TRIM33 as an Essential Regulator of Dendritic Cell Differentiation

Authors

Ioanna Tiniakou
Pei-Feng Hsu
Lorena S Lopez-Zepeda
Görkem Garipler
Eduardo Esteva
Nicholas M Adams
Geunhyo Jang
Chetna Soni
Colleen M Lau
Fan Liu
Alireza Khodadadi-Jamayran
Tori C Rodrick
Drew Jones
Aristotelis Tsirigos
Uwe Ohler
Mark T Bedford
Stephen D Nimer
Vesa Kaartinen
Esteban O Mazzoni
Boris Reizis

Publication Date

4-12-2024

Journal

Science Immunology

Abstract

The development of dendritic cells (DCs), including antigen-presenting conventional DCs (cDCs) and cytokine-producing plasmacytoid DCs (pDCs), is controlled by the growth factor Flt3 ligand (Flt3L) and its receptor Flt3. We genetically dissected Flt3L-driven DC differentiation using CRISPR-Cas9-based screening. Genome-wide screening identified multiple regulators of DC differentiation including subunits of TSC and GATOR1 complexes, which restricted progenitor growth but enabled DC differentiation by inhibiting mTOR signaling. An orthogonal screen identified the transcriptional repressor Trim33 (TIF-1γ) as a regulator of DC differentiation. Conditional targeting in vivo revealed an essential role of Trim33 in the development of all DCs, but not of monocytes or granulocytes. In particular, deletion of Trim33 caused rapid loss of DC progenitors, pDCs, and the cross-presenting cDC1 subset. Trim33-deficient Flt3

Keywords

Cell Differentiation, Chorea, Cytokines, Dendritic Cells

Comments

Supplementary Materials

PMID: 38608038