Single-cell analysis reveals immune cell abnormalities underlying the clinical heterogeneity of patients with systemic sclerosis
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<sup>+</sup> CD14<sup>+</sup> 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<sup>+</sup> 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.
Authors
- Kazunori Inoue (ORCID: https://orcid.org/0000-0002-7149-6651)
- Kohei Tsujimoto (ORCID: https://orcid.org/0000-0001-6958-2983)
- Kunihiro Hattori
- Yoshitaka Isaka (ORCID: https://orcid.org/0000-0002-0820-7167)
- Ryusuke Omiya
- Atsushi Takahashi (ORCID: https://orcid.org/0000-0002-5182-4320)
- Yoichi Kakuta (ORCID: https://orcid.org/0000-0001-5339-4312)
- Hachiro Konaka
- S. Kawada (ORCID: https://orcid.org/0000-0001-9679-5925)
- Shoichi Metsugi
- Atsushi Kumanogoh (ORCID: https://orcid.org/0000-0003-4749-7117)
- Masayuki Nishide (ORCID: https://orcid.org/0000-0001-6060-1228)
- Yukinori Okada (ORCID: https://orcid.org/0000-0002-0311-8472)
- Tetsuo Takehara (ORCID: https://orcid.org/0000-0001-5036-3457)
- Masashi Narazaki (ORCID: https://orcid.org/0000-0002-5613-4409)
- Hiroshi Shimagami (ORCID: https://orcid.org/0000-0001-7820-364X)
- Nachi Ishikawa
- Ryuya Edahiro (ORCID: https://orcid.org/0000-0001-5009-6408)
- Jun Fujimoto
- Eri Itotagawa (ORCID: https://orcid.org/0000-0003-0263-1108)
- Kensuke Mitsumoto
- Daisuke Nakatsubo (ORCID: https://orcid.org/0009-0004-0517-0874)
- Kazuki Matsukawa
- Maiko Naito (ORCID: https://orcid.org/0000-0002-4360-7043)
- Tomoko Namba‐Hamano (ORCID: https://orcid.org/0000-0002-6049-7616)
- Hayato Hikita (ORCID: https://orcid.org/0000-0003-2488-7315)
- Norio Nonomura (ORCID: https://orcid.org/0000-0002-6522-6233)
- Yasuhiro Kato (ORCID: https://orcid.org/0000-0002-4050-2350)
- Masayuki Mizui (ORCID: https://orcid.org/0000-0003-2543-8108)
- Shigeaki Nakazawa (ORCID: https://orcid.org/0000-0001-5857-3483)
- Kei Nishimura
- Hiroaki Matsushita (ORCID: https://orcid.org/0000-0003-2899-5313)
- Takahiro Kawasaki (ORCID: https://orcid.org/0000-0002-8625-7899)
- Shinji Higa
- Seiya Kato (ORCID: https://orcid.org/0009-0005-9116-9729)
Institutions
- Japan Agency for Medical Research and Development (JP)
- RIKEN Center for Integrative Medical Sciences (JP)
- Nippon Medical School Hospital (JP)
- Osaka International University (JP)
- The University of Tokyo (JP)
- The University of Osaka (JP)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-06-17
- DOI
- https://doi.org/10.1038/s41467-025-60034-7
- Citations
- 9
- Primary Topic
- Systemic Sclerosis and Related Diseases
- Type
- article
- Field-Weighted Citation Impact
- 13.24
Funders
- Japan Agency for Medical Research and Development
- Ono Pharmaceutical
- Japan Society for the Promotion of Science
- Japan Science and Technology Agency
- Core Research for Evolutional Science and Technology
- Moonshot Research and Development Program