Macrophages Gain Attention as Psoriasis Research Evolves

New analyses of psoriasis research suggest that macrophages—immune cells once viewed primarily as supporting players in inflammation—have become a central focus in efforts to better understand disease progression and identify future therapeutic targets.¹

In a bibliometric analysis published in Frontiers in Medicine, investigators reviewed 2012 publications published between 2015 and 2024 that examined the relationship between macrophages and psoriasis. The findings illustrated a shift in psoriasis research away from an exclusive focus on T cells and toward broader exploration of innate immunity, inflammatory signaling pathways, and precision medicine approaches.

Psoriasis affects an estimated 125 million people worldwide and is characterized by chronic inflammation, keratinocyte hyperproliferation, and immune dysregulation. Although adaptive immune pathways have historically dominated psoriasis research and treatment development, recent evidence has increasingly implicated macrophages in disease initiation, maintenance, and resolution.

The investigators at the China-Japan Friendship Hospital in Beijing analyzed literature retrieved from the Web of Science and Scopus databases using bibliometric software platforms, including CiteSpace and VOSviewer. The review included English-language articles and review articles published between January 1, 2015, and December 31, 2024.

Publication activity increased substantially during the study period, rising from 108 publications in 2015 to a peak of 300 in 2022 before declining modestly to 268 publications in 2024. According to the authors, the trend reflected growing recognition of macrophages’ role in psoriasis pathogenesis.

China produced the largest number of publications, accounting for 503 articles, followed by the US with 455 articles. However, US publications demonstrated higher citation impact, averaging 61.7 citations per article compared with 29.18 citations for Chinese publications. Germany, Italy, Japan, and the UK also ranked among the top contributors.

The analysis also identified major shifts in research priorities over time. Early investigations focused largely on inflammatory mediators such as tumor necrosis factor (TNF)-α and Th17 cells. Between 2017 and 2020, research emphasis shifted toward cellular mechanisms and biologic therapies, including studies involving etanercept. More recent research has concentrated on transcriptomics, STAT3 signaling, angiogenesis, and precision medicine approaches.

Several molecular pathways emerged as dominant themes. TNF-α, interleukin (IL)-17, and IL-6 were among the most frequently studied cytokines, underscoring their importance in macrophage-mediated inflammatory signaling. IL-17 demonstrated particularly high centrality within the research network, reflecting its broad relevance across psoriasis studies.

The investigators also highlighted growing interest in macrophage polarization, particularly the balance between pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages. During active psoriasis, M1 macrophages predominate and release cytokines, including TNF-α, IL-1β, IL-6, and IL-23, which contribute to keratinocyte proliferation and inflammatory amplification. M2 macrophages, by contrast, appear to support tissue repair and inflammation resolution.²

Despite increasing attention to macrophages overall, the authors found that relatively little research focused specifically on M2-mediated anti-inflammatory pathways.¹ Only 23 publications—approximately 1.1% of the reviewed literature—explicitly investigated M2 macrophages in psoriasis.

The researchers argued that this imbalance may represent a missed opportunity for future therapeutic development.

“Promoting M2 polarization or enhancing endogenous anti-inflammatory pathways might complement current suppressive therapies,” the authors wrote.

The study additionally identified gaps in translational research. Although preclinical mechanistic studies and clinical trials were common, only 12% of publications specifically addressed biomarker development or patient stratification strategies intended to bridge laboratory findings and clinical implementation.

The investigators also noted increasing use of advanced technologies such as spatial transcriptomics and single-cell RNA sequencing, both which have revealed previously unrecognized macrophage heterogeneity in psoriatic skin. These findings may eventually help refine therapeutic targeting beyond the traditional M1/M2 framework.

The authors acknowledged several study limitations, including restriction to English-language publications and reliance on bibliometric indicators that may reflect citation trends rather than research quality. They also noted that the analysis could not account for unpublished negative findings or fully evaluate broader psoriasis literature outside macrophage-focused studies.

The investigators concluded that macrophages have emerged as “master regulators” in psoriasis pathogenesis and may represent an important frontier for future precision therapies.

References

1. Yu H, Wang Y, Huang Q, Meng L, Tao J, Bai Y. Macrophages in psoriasis: a bibliometric analysis of research trends, knowledge gaps, and future directions (2015-2024). Front Med. 2026;13:1737689. doi:10.3389/fmed.2026.1737689
2. Nazimek K, Bryniarski K. Macrophage functions in psoriasis: lessons from mouse models. Int J Mol Sci. 2024;25(10):5306. doi:10.3390/ijms25105306