Department of Orthopedic Surgery, Columbia University, New York, NY, 10032, USA.
Department Orthopedics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Sci Rep. 2024 Nov 5;14(1):26839. doi: 10.1038/s41598-024-77958-7.
Autoimmunity underlies many painful disorders, such as enthesopathies, which localize to the enthesis. From infiltration of the synovium and axial skeleton by B cells, to disturbances in the ratio of M1/M2 enthesis macrophages, to CD8 + T cell mediated inflammation, autoimmune dysregulation is becoming increasingly well characterized in enthesopathies. Tissue resident B cells, macrophages, neutrophils, and T cells have also been localized in healthy human entheses. However, the potential developmental origins, presence, and role of immune cells (ICs) in enthesis development is not known. Here, we use single-cell RNA-sequencing analysis to describe IC subtypes present in the enthesis before, during, and after mineralization, and to infer regulatory interactions between ICs and mesenchymal cells (MCs). We report the presence of nine phenotypically distinct IC subtypes, including B cells, macrophages, neutrophils, and T cells. We find that specific IC subtypes may promote MC-proliferation and differentiation, and that MCs may regulate IC phenotype and autoimmunity. Our findings suggest that bidirectional regulatory interactions between ICs and MCs may be important to enthesis mineralization, and suggest that progenitor MCs have a unique ability to limit autoimmunity during development.
自身免疫是许多疼痛性疾病的基础，例如附着病，其定位于附着处。从 B 细胞浸润滑膜和轴性骨骼，到 M1/M2 附着处巨噬细胞比例紊乱，再到 CD8+T 细胞介导的炎症，自身免疫失调在附着病中的特征越来越明显。组织驻留的 B 细胞、巨噬细胞、中性粒细胞和 T 细胞也已在健康人的附着处定位。然而，免疫细胞（ICs）在附着处发育中的潜在发育起源、存在和作用尚不清楚。在这里，我们使用单细胞 RNA 测序分析来描述在矿化之前、期间和之后附着处存在的 IC 亚型，并推断 ICs 和间充质细胞（MCs）之间的调节相互作用。我们报告了存在九种表型不同的 IC 亚型，包括 B 细胞、巨噬细胞、中性粒细胞和 T 细胞。我们发现特定的 IC 亚型可能促进 MC 的增殖和分化，而 MC 可能调节 IC 的表型和自身免疫。我们的研究结果表明，ICs 和 MCs 之间的双向调节相互作用可能对附着处矿化很重要，并表明祖细胞 MCs 在发育过程中具有独特的限制自身免疫的能力。
