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

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 () and Masayuki Nishide ()
Additional contact information
Hiroshi Shimagami: Osaka University
Kei Nishimura: Osaka University
Hiroaki Matsushita: Osaka University
Shoichi Metsugi: Osaka University
Yasuhiro Kato: Osaka University
Takahiro Kawasaki: Osaka University
Kohei Tsujimoto: Osaka University
Ryuya Edahiro: Osaka University
Eri Itotagawa: Osaka University
Maiko Naito: Osaka University
Shoji Kawada: Osaka University
Daisuke Nakatsubo: Osaka University
Kazuki Matsukawa: Osaka University
Tomoko Namba-Hamano: Osaka University
Kazunori Inoue: Osaka University
Atsushi Takahashi: Osaka University
Masayuki Mizui: Osaka University
Seiya Kato: Osaka University
Hayato Hikita: Osaka University
Shigeaki Nakazawa: Osaka University
Yoichi Kakuta: Osaka University
Hachiro Konaka: Nippon Life Hospital
Kensuke Mitsumoto: Nippon Life Hospital
Nachi Ishikawa: Osaka International Medical & Science Center
Jun Fujimoto: Osaka International Medical & Science Center
Shinji Higa: Osaka International Medical & Science Center
Ryusuke Omiya: Osaka University
Yoshitaka Isaka: Osaka University
Tetsuo Takehara: Osaka University
Norio Nonomura: Osaka University
Yukinori Okada: Osaka University
Kunihiro Hattori: Osaka University
Masashi Narazaki: Osaka University
Atsushi Kumanogoh: Osaka University
Masayuki Nishide: Osaka University

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-60034-7

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