Single-cell analysis in rheumatic and allergic diseases: insights for clinical practice

Nishide, Masayuki; Shimagami, Hiroshi; Kumanogoh, Atsushi

doi:10.1038/s41577-024-01043-3

Nat Rev Immunol

2024

DOI: 10.1038/s41577-024-01043-3

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Single-cell analysis in rheumatic and allergic diseases: insights for clinical practice

Masayuki Nishide,

Hiroshi Shimagami,

Atsushi Kumanogoh

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2024

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Cited by 1 publication

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Single-cell analysis reveals immune cell abnormalities underlying the clinical heterogeneity of systemic sclerosis

Nishide,

Shimagami,

Nishimura

et al. 2024

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Autoimmune rheumatic diseases present with diverse clinical manifestations that often complicate management strategies. Systemic sclerosis (SSc) is a representative disease with multiple organ manifestations affecting patients worldwide, and exploring the variation of immune abnormalities in this disease is of great interest. However, previous studies have focused on diseased tissues, and it remains largely unknown how cellular diversity links to clinical heterogeneity. Here, we perform single-cell transcriptome and surface proteome analyses of peripheral blood mononuclear cells (PBMCs) from 21 SSc patients who are not receiving immunomodulatory therapy and show that different clinical manifestations are associated with distinct immune abnormalities. Enrichment of a specific CD14+ monocyte subset characterized by EGR1 expression is observed in patients with scleroderma renal crisis (SRC). Integrated analysis of PBMCs and kidney biopsy cells indicates that this monocyte subset directly differentiates into tissue-damaging macrophages under activation of NF-κB signaling. Clinically, EGR1 expression in monocytes is significantly upregulated at the onset of SRC and decreases after treatment, suggesting its potential as a biomarker for SRC. In patients with interstitial lung disease (ILD), a CD8+ T cell subset with type II interferon signature is highly enriched in both peripheral blood and lung tissue of patients with progressive disease, suggesting that chemokine-driven migration of these cells is involved in ILD progression. Thus, distinct immune cell profiles at the single cell level reveal different directions of immune dysregulation between organ manifestations and provide insights for tailored treatment strategies.

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Single-cell analysis reveals immune cell abnormalities underlying the clinical heterogeneity of systemic sclerosis

Nishide,

Shimagami,

Nishimura

et al. 2024

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Single-cell analysis in rheumatic and allergic diseases: insights for clinical practice

Cited by 1 publication

References 136 publications

Single-cell analysis reveals immune cell abnormalities underlying the clinical heterogeneity of systemic sclerosis

Single-cell analysis reveals immune cell abnormalities underlying the clinical heterogeneity of systemic sclerosis

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