Dataset Information

Bulk RNA sequencing in Mouse Bone Marrow-Derived Macrophages Following CD74 Deficiency

ABSTRACT: Following CD74 knockout in mouse bone marrow-derived macrophages (BMDMs), we employed bulk RNA sequencing to systematically profile transcriptomic changes, with a particular focus on alterations in key regulatory elements. Building on these findings, we further investigated the potential molecular mechanisms through which CD74 modulates signaling pathways in macrophages, aiming to uncover its regulatory roles in immune responses and macrophage functional plasticity.

ORGANISM(S): Mus musculus

PROVIDER: GSE328279 | GEO | 2026/04/23

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:CD74 is a cell-surface receptor for the cytokine macrophage migration inhibitory factor (MIF). MIF binding to CD74 induces a signaling cascade resulting in the release of its cytosolic intracellular domain (CD74-ICD), which regulates transcription in naive B and chronic lymphocytic leukemia (CLL) cells. In the current study, we investigated the role of CD74 in the regulation of the immunosuppressive tumor microenvironment (TME) in triple-negative breast cancer (TNBC). TNBC is the most aggressive breast cancer subtype, in which there is a massive infiltration of immune cells to the tumor microenvironment, making this tumor a good candidate for immunotherapy. The tumor and immune cells in TNBC express high levels of CD74, however, the function of this receptor in this environment was not fully characterized. Regulatory B cells (Bregs) and tolerogenic dendritic cells )tol-DCs( were previously shown to attenuate the antitumor immune response in TNBC. Here, we demonstrate that CD74 enhances tumor growth by inducing the expansion of tumor-infiltrating tol-DCs and Bregs. Utilizing CD74-KO mice, conditionally CD74 -/- Cre-flox mice lacking CD74 in CD23+ mature B cells and mice lacking CD74 in the CD11c+ population and a CD74 inhibitor (DRQ), revealed that MIF secreted from the tumor cells activate CD74 expressed on DCs. This activation induces the binding of CD74-ICD to the SP1 promotor, resulting in the upregulation of SP1 expression. SP1 binds the IL-1β promotor, leading to the downregulation of its transcription. The reduced levels of IL-1β lead to decreased anti-tumor activity by allowing expansion of the tol-DC, which induce the expansion of the Breg population, suggesting the cross-talk between these two populations. Taken together, these results suggest that CD74+ CD11c+ DCs are the dominant cell type involved in the regulation of the TNBC progression. These findings indicate that CD74 might serve as a novel therapeutic target in triple-negative breast cancer.

Dataset Information

Bulk RNA sequencing in Mouse Bone Marrow-Derived Macrophages Following CD74 Deficiency

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets