# Regulation and Mechanism of Deleted in Breast Cancer‐1 on Dendritic Cell Function in Systemic Lupus Erythematosus

## TL;DR

This study explores how DBC1 affects dendritic cells in lupus, showing that reducing DBC1 can ease symptoms by altering immune responses.

## Contribution

The novel finding is that DBC1 deficiency in dendritic cells ameliorates lupus by suppressing proinflammatory signals and promoting regulatory T cells.

## Key findings

- DBC1 deficiency in dendritic cells reduces autoantibodies and Tfh cells in lupus models.
- DBC1 deficiency lowers proinflammatory cytokines and STAT5 signaling in dendritic cells.
- Overexpression of STAT5 negates the protective effects of DBC1 deficiency in lupus.

## Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting multiple organs and involving both innate and adaptive immunity. Dendritic cells (DCs) play a crucial role in linking innate and adaptive immune responses, and therefore they deeply participate in the initiation and development of SLE. Deleted in breast cancer‐1 (DBC1) is a negative regulator of deacetylase SIRT1 (the mammalian homolog of silent information regulator 1) and involves in tissue inflammation. Roles of DBC1 in immune cells remain largely unknown, especially in DCs. We here identified that DBC1 is upregulated in activated DCs, and DBC1 deficiency weakened DC maturation while promoting B7‐H1 expression. DC conditional knockout of DBC1 ameliorated murine lupus pathology by decreasing autoantibodies, complement C3, plasma cells, and follicular T helper (Tfh) cells, whereas promoting regulatory T‐cell development. We further demonstrated that Dbc1−/−
DC lowered proinflammatory cytokine secretion such as IL‐4, IL‐6, and IL‐12, and reduced signal transducer and activator of transcription 5 (STAT5) signal. With STAT5 overexpression, the protective effect by Dbc1−/−
DC was abolished in the lupus model. Therefore, targeting the DBC1‐STAT5 axis in DCs diversifies the therapeutic strategies for SLE.

LPS‐stimulated DC activation upregulated DBC1. DBC1‐deficient DC ameliorated murine SLE symptoms. DBC1 deficiency suppressed immune responses in DC. DBC1 deficiency lowered STAT5 expression and subsequent phosphorylation. STAT5 overexpression abolished murine SLE remission primed by DBC1 deficiency.