B7-H3 (CD276) regulates myeloid-derived suppressor cell differentiation in pulmonary fibrosis
Year: 2026
Type: article
Abstract: Introduction Myeloid-derived suppressor cells (MDSCs) are elevated in cancer, chronic inflammation and fibrosis. The immune checkpoint molecule B7-H3 (CD276) is upregulated in fibrotic conditions and has been implicated in the expansion and recruitment of MDSCs to the fibrotic lung; however, the underlying mechanism remains unclear. Methods To investigate the role of B7-H3 in MDSC induction, myeloid differentiation and lung fibrosis, we employed in vivo B7-H3 blockade, cell type-specific deletion mouse models, exogenous B7-H3 administration, and in vitro bone marrow differentiation assays. Results Our results showed that in vivo B7-H3 blockade, and cell type-specific deletion of B7-H3 in collagen-expressing or myeloid cells attenuated lung fibrosis. Reduction of B7-H3 was associated with decreased MDSC expansion and increased numbers of MHCII + F4/80 + cells. In contrast, exogenous B7-H3 administration in vivo reduced MHCII + F4/80 + cells in the lung. In vitro , treatment of bone marrow cells with B7-H3 promoted MDSC generation and inhibited myeloid differentiation. Additionally, we found that soluble B7-H3, potentially cleaved from fibroblasts by matrix metalloproteinases (MMPs), contributed to the induction of MDSCs in co-cultured bone marrow cells and the suppression of myeloid cell differentiation. Finally, CD84, a novel immunosuppressive marker for M-MDSCs, expressed on MDSCs was required for B7-H3-mediated enhancement of their immunosuppressive capacity toward T cells. Discussion Together, these findings reveal that bleomycin-induced B7-H3 signals to the bone marrow, skewing myeloid differentiation toward an immature MDSC phenotype by inhibiting normal myeloid maturation during fibrosis.
Source: Frontiers in Immunology
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7202040838