Shimagami Hiroshi, Nishimura Kei, Matsushita Hiroaki, Metsugi Shoichi, Kato Yasuhiro, Kawasaki Takahiro, Tsujimoto Kohei, Edahiro Ryuya, Itotagawa Eri, Naito Maiko, Kawada Shoji, Nakatsubo Daisuke, Matsukawa Kazuki, Namba-Hamano Tomoko, Inoue Kazunori, Takahashi Atsushi, Mizui Masayuki, Kato Seiya, Hikita Hayato, Nakazawa Shigeaki, Kakuta Yoichi, Konaka Hachiro, Mitsumoto Kensuke, Ishikawa Nachi, Fujimoto Jun, Higa Shinji, Omiya Ryusuke, Isaka Yoshitaka, Takehara Tetsuo, Nonomura Norio, Okada Yukinori, Hattori Kunihiro, Narazaki Masashi, Kumanogoh Atsushi, Nishide Masayuki
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Department of Immunopathology, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), Osaka University, Suita, Osaka, Japan.
Nat Commun. 2025 Jun 17;16(1):4949. doi: 10.1038/s41467-025-60034-7.
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.
自身免疫性疾病系统性硬化症（SSc）表现出多种器官表现，这常常使治疗策略复杂化。为了探索免疫细胞亚群的变化及其与临床异质性的联系，我们对21例从未接受过免疫抑制治疗的SSc患者的外周血单个核细胞（PBMC）进行了单细胞分析。我们在硬皮病肾危象（SRC）患者中鉴定出一个EGR1+ CD14+单核细胞亚群。该亚群激活NF-κB信号通路并分化为造成组织损伤的巨噬细胞，这些巨噬细胞在组织损伤部位积聚。此外，我们在进行性间质性肺病（ILD）患者的外周血和肺组织中鉴定出一个具有II型干扰素特征的CD8+ T细胞亚群，这表明趋化因子驱动的这些细胞迁移促成了ILD的进展。因此，我们的单细胞分析揭示了与临床器官表现相关的独特免疫细胞异常，为定制治疗策略提供了见解。
