Single-cell analysis reveals transcriptomic patterns in active macrophage activation syndrome and therapeutic potential of albumin-fused interleukin-10 in a mouse model
Abstract
IntroductionHemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening hyperinflammatory conditions. We aimed to characterize immune cell transcriptomic patterns in human MAS and investigate the therapeutic potential of albumin-fused IL-10 protein (SA-IL-10) in a MAS mouse model.MethodsWe performed single-cell RNA sequencing (scRNA-seq) on bone marrow and peripheral blood samples from patients with newly developed MAS caused by diverse etiologies. We generated paired Seq-Well single-cell transcriptomes from bone marrow and blood of patients with active HLH/MAS. In the absence of a contemporaneous control cohort, technology-matched public Seq-Well marrow and same-laboratory control blood were projected onto the frozen patient atlases as lineage context, not as a case–control comparison. We also evaluated the effect of SA-IL-10 in a CpG-DNA–induced mouse model of MAS.ResultsHuman scRNA-seq identified diverse immune cell populations, including dendritic cells, macrophages, and monocyte subsets. Canonical lineages in the public data were transferred to the expected patient states. Monocyte 1 and macrophage populations expressed transcripts encoding IL-10 receptor subunits and associated signaling molecules, although these findings reflect RNA abundance and do not establish functional responsiveness. Donor-level phagocytosis and interferon-γ programs showed no significant differences after multiple-testing correction. In the mouse model, SA-IL-10 treatment significantly improved anemia, leukocytopenia, splenomegaly, and liver dysfunction and was associated with reduced circulating interferon-γ levels and bone marrow macrophage abundance.ConclusionHuman scRNA-seq provides transcriptomic patterns in active HLH/MAS. The therapeutic effects observed in the mouse model support further investigation of SA-IL-10 as a potential treatment for MAS.
Related
- A cell death screen identifies macrophage-depleting agents with therapeutic potential
- Complement activation in immune thrombotic thrombocytopenic purpura: Possible amplifier and potential therapeutic opportunity.
- Interferon regulatory factor 1: a key transcriptional node orchestrating macrophage polarization: mechanisms and therapeutic potential
- Damage-Associated Molecular Patterns and Trained Immunity of Monocyte-Macrophage Populations in Osteoarthritis: Potential Molecular Links and Therapeutic Opportunities.
- Macrophage-mediated bystander T cell activation in varicose veins
BibTeX
@article{fujii2026singlecell,
title = {{Single-cell analysis reveals transcriptomic patterns in active macrophage activation syndrome and therapeutic potential of albumin-fused interleukin-10 in a mouse model}},
author = {Wataru Fujii and Hideaki Sofue and Eiji Yuba and Jun Ishihara and Kevin Baßler and Anna Hasegawa and Tomoka Hiyama and Sara Komatsu and Kaito Nakamura and Ayae Tanaka and Satoko Arai and Reika Maezawa and Masafumi Arima and Kazuhiro Kurasawa and Takayoshi Owada and Yuri Kamitsuji and Nobuhiko Uoshima and Tsutomu Kobayashi and Hitoji Uchiyama and Shinsuke Mizutani and Junya Kuroda and Yutaka Kawahito and Kei Ikeda},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1890134},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1890134},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Single-cell analysis reveals transcriptomic patterns in active macrophage activation syndrome and therapeutic potential of albumin-fused interleukin-10 in a mouse model
AU - Wataru Fujii
AU - Hideaki Sofue
AU - Eiji Yuba
AU - Jun Ishihara
AU - Kevin Baßler
AU - Anna Hasegawa
AU - Tomoka Hiyama
AU - Sara Komatsu
AU - Kaito Nakamura
AU - Ayae Tanaka
AU - Satoko Arai
AU - Reika Maezawa
AU - Masafumi Arima
AU - Kazuhiro Kurasawa
AU - Takayoshi Owada
AU - Yuri Kamitsuji
AU - Nobuhiko Uoshima
AU - Tsutomu Kobayashi
AU - Hitoji Uchiyama
AU - Shinsuke Mizutani
AU - Junya Kuroda
AU - Yutaka Kawahito
AU - Kei Ikeda
PY - 2026
DA - 2026/11/02
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1890134
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1890134
AB - IntroductionHemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening hyperinflammatory conditions. We aimed to characterize immune cell transcriptomic patterns in human MAS and investigate the therapeutic potential of albumin-fused IL-10 protein (SA-IL-10) in a MAS mouse model.MethodsWe performed single-cell RNA sequencing (scRNA-seq) on bone marrow and peripheral blood samples from patients with newly developed MAS caused by diverse etiologies. We generated paired Seq-Well single-cell transcriptomes from bone marrow and blood of patients with active HLH/MAS. In the absence of a contemporaneous control cohort, technology-matched public Seq-Well marrow and same-laboratory control blood were projected onto the frozen patient atlases as lineage context, not as a case–control comparison. We also evaluated the effect of SA-IL-10 in a CpG-DNA–induced mouse model of MAS.ResultsHuman scRNA-seq identified diverse immune cell populations, including dendritic cells, macrophages, and monocyte subsets. Canonical lineages in the public data were transferred to the expected patient states. Monocyte 1 and macrophage populations expressed transcripts encoding IL-10 receptor subunits and associated signaling molecules, although these findings reflect RNA abundance and do not establish functional responsiveness. Donor-level phagocytosis and interferon-γ programs showed no significant differences after multiple-testing correction. In the mouse model, SA-IL-10 treatment significantly improved anemia, leukocytopenia, splenomegaly, and liver dysfunction and was associated with reduced circulating interferon-γ levels and bone marrow macrophage abundance.ConclusionHuman scRNA-seq provides transcriptomic patterns in active HLH/MAS. The therapeutic effects observed in the mouse model support further investigation of SA-IL-10 as a potential treatment for MAS.
SN - 1664-3224
ER -