Cutting Edge: ACVRL1 Signaling Augments CD8α+ Dendritic Cell Development

Abstract

Dendritic cells (DCs) are a collection of different subtypes, each of which is characterized by specific surface markers, gene-expression patterns, and distinct functions. Members of the IFN regulatory factor family play critical roles in DC development and functions. Recently, Irf8 was shown to activate TGF-β signaling, which led to exacerbated neuroinflammation in the experimental autoimmune encephalomyelitis mouse model. We analyzed the effect of Irf8 on TGF-β/bone morphogenetic protein pathway–specific genes in DCs and identified Acvrl1, a type I TGF-β superfamily receptor, as a gene strongly induced by Irf8 expression. Among various DC subtypes, Acvrl1 is differentially expressed in CD8α+ DCs. ACVRL1 signaling augmented Irf8-directed classical CD8α+ DC development. Irf8 expression is essential for plasmacytoid DC and CD8α+ DC development, and this study demonstrates that ACVRL1 signaling plays a pivotal role whereby it suppresses plasmacytoid DC development while enhancing that of CD8α+ DCs, thus contributing to DC diversity development.

Aged Callus Skeletal Stem/Progenitor Cells Contain an Inflammatory Osteogenic Population With Increased IRF and NF-κB Pathways and Reduced Osteogenic Potential

“…Among the inferred target genes of cluster 1.1 that did not overlap with cluster 1.2, Irf2bp2 has been identified as a repressor for IRF2 signaling ( Ramalho-Oliveira et al, 2019 ). In contrast, among the five target genes of cluster 1.2 that were not inferred in cluster 1.1, Cebpb ( Pal et al, 2009 ), Acvrl1 ( Verma et al, 2016 ), Anxa1 ( Yap et al, 2020 ), and Upp1 ( Yan et al, 2016 ) have been reported to be related to IRF signaling and inflammation in various disease models, supporting the argument that cluster 1.2 has the inflammatory osteogenic progenitors mediated by IRF signaling ( Supplementary Figure S8 ).…”

Regulation of the Immune System in Health and Disease by Members of the Bone Morphogenetic Protein Family

“…Furthermore, moDCs treated with BMP4 displayed increased immunosuppressive functionality by expressing higher levels of IL-10 and TGFβ ( 13 ). In mice, BMP9 was shown to promote CD8α + DC differentiation and inhibit plasmacytoid DC (pDC) development in a process that is mediated through ACVRL1 ( 14 ).…”

GeneNetwork: a continuously updated tool for systems genetics analyses

“…Most notably of those, Acvrl1 and St18 which are both involved in cytokine release in the immune system. Acvrl1 signaling is responsible for dendritic cell development within the cytotoxic T cell (CD8 + ) subtype (Verma et al, 2016). This signaling is also related to inflammatory pathways, similarly to RANTES.…”