Research Background
Study Overview
Psoriasis is a chronic immune-mediated skin disease characterized by persistent inflammation and recurrent skin lesions. Although therapies targeting downstream inflammatory pathways, particularly the IL-23/IL-17 axis, have substantially improved disease management, upstream immune cell populations capable of sustaining or reactivating inflammation may remain.
The mononuclear phagocyte system (MPS), which includes monocytes, macrophages, and dendritic cells, plays an important role in coordinating inflammatory responses. A recent study published in Theranostics investigated whether specific MPS populations expressing high levels of colony-stimulating factor 1 receptor (CSF1R) act as upstream drivers of psoriasis and explored how CSF1R signaling affects the resolution of inflammation.
Study Design
An Integrated Research Strategy
The researchers combined human single-cell and spatial transcriptomic analyses with imiquimod-induced mouse models of psoriasis. Genetic and pharmacological interventions were used to compare the effects of local and systemic CSF1R targeting and to investigate the downstream relationship between CSF1R and peroxisome proliferator-activated receptor alpha (PPARα).
Bulk RNA sequencing of murine skin samples was also incorporated to characterize gene expression changes associated with reduced CSF1R activity. This integrated approach connected cellular and spatial observations with transcriptomic evidence and functional validation.
Research Highlights
Key Findings
Pathogenic CSF1R-high MPS Cells Form Inflammatory Hubs
The study identified an expanded population of pathogenic CSF1R-high MPS cells in psoriatic lesions. These cells formed localized inflammatory hubs enriched in key cytokines, including TNF-α, IL-1β, and IL-23.
The researchers also found that increased CSF1 expression reinforced MPS activation through autocrine signaling, helping these inflammatory cell populations maintain and amplify local immune responses.
Systemic CSF1R Targeting More Effectively Disrupts Inflammatory Networks
Compared with local intervention, systemic CSF1R targeting more effectively reduced pathogenic MPS populations across both skin and blood compartments.
By disrupting the connection between tissue-resident and circulating inflammatory cells, systemic targeting depleted pathogenic hubs and produced broader suppression of pro-inflammatory cytokine activity. These findings highlight the importance of the skin–blood MPS circuit in maintaining psoriatic inflammation.
PPARα Functions as a Critical Downstream Regulator
Mechanistic analyses showed that CSF1R activation directly suppressed PPARα, a regulator involved in lipid metabolism and the resolution of inflammation.
Inhibiting CSF1R restored PPARα-mediated inflammation-resolving programs. Importantly, blocking PPARα abolished the anti-inflammatory effects of CSF1R inhibition, supporting its essential downstream role in the CSF1R–PPARα signaling axis.
Research Significance
Implications for Psoriasis Research
This study positions pathogenic CSF1R-high MPS hubs as upstream organizers of psoriatic inflammation rather than passive responders to inflammatory cytokines. It also identifies PPARα suppression as an important mechanism through which CSF1R signaling prevents the effective resolution of inflammation.
Together, these findings provide a mechanistic foundation for therapeutic strategies that target pathogenic myeloid networks while restoring endogenous inflammation-resolving programs. As the current evidence is primarily mechanistic and preclinical, further studies will be required to evaluate the safety and effectiveness of systemic CSF1R targeting in patients.
BMKGENE Contribution
Supporting Transcriptomic Profiling and Bioinformatics Analysis
BMKGENE provided bulk RNA sequencing and bioinformatics analysis services for murine skin samples in this study. The resulting transcriptomic data supported differential gene expression and pathway enrichment analyses, helping characterize the molecular changes associated with reduced CSF1R activity and identify the involvement of PPAR signaling.
Bulk RNA Sequencing · Bioinformatics Analysis
Original Publication
Lin, Z.-J., Li, Y., Yu, Y., et al. Theranostics 16(8), 4336–4357 (2026). DOI: 10.7150/thno.128248.
Post time: Aug-20-2026
