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

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

Abstract The autoimmune disease systemic sclerosis (SSc) presents with multiple organ manifestations that often complicate management strategies. To explore variations in immune cell subsets and their link to clinical heterogeneity, here we perform single-cell profiling of peripheral blood mononucle...

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Main Authors: Hiroshi Shimagami, Kei Nishimura, Hiroaki Matsushita, Shoichi Metsugi, Yasuhiro Kato, Takahiro Kawasaki, Kohei Tsujimoto, Ryuya Edahiro, Eri Itotagawa, Maiko Naito, Shoji Kawada, Daisuke Nakatsubo, Kazuki Matsukawa, Tomoko Namba-Hamano, Kazunori Inoue, Atsushi Takahashi, Masayuki Mizui, Seiya Kato, Hayato Hikita, Shigeaki Nakazawa, Yoichi Kakuta, Hachiro Konaka, Kensuke Mitsumoto, Nachi Ishikawa, Jun Fujimoto, Shinji Higa, Ryusuke Omiya, Yoshitaka Isaka, Tetsuo Takehara, Norio Nonomura, Yukinori Okada, Kunihiro Hattori, Masashi Narazaki, Atsushi Kumanogoh, Masayuki Nishide
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60034-7
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Summary:Abstract The autoimmune disease systemic sclerosis (SSc) presents with multiple organ manifestations that often complicate management strategies. To explore variations in immune cell subsets and their link to clinical heterogeneity, here we perform single-cell profiling of peripheral blood mononuclear cells (PBMC) from 21 SSc patients who never received immunosuppressive therapy. We identify a subset of EGR1 + CD14+ monocytes in patients with scleroderma renal crisis (SRC). This subset activates NF-kB signaling and differentiates into tissue-damaging macrophages, which accumulate at sites of tissue injury. Furthermore, we identify a CD8+ T cell subset with type II interferon signature in the peripheral blood and the lung tissue of patients with progressive interstitial lung disease (ILD), suggesting that chemokine-driven migration of these cells contributes to ILD progression. Thus, our single-cell analysis reveals distinct immune cell abnormalities associated with clinical organ manifestations, providing insights into tailored treatment strategies.
ISSN:2041-1723

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