Fibroblasts reside in various organs and support tissue structure and homeostasis under physiological conditions. Phenotypic alterations of fibroblasts underlie the development of diverse pathological conditions, including organ fibrosis. Recent advances in single-cell biology have revealed that fibroblasts comprise heterogeneous subpopulations with distinct phenotypes, which exert both beneficial and detrimental effects on the host organs in a context-dependent manner. In the kidney, phenotypic alterations of resident fibroblasts provoke common pathological conditions of chronic kidney disease (CKD), such as renal anemia and peritubular capillary loss. Additionally, in aged injured kidneys, fibroblasts provide functional and structural supports for tertiary lymphoid tissues (TLTs), which serve as the ectopic site of acquired immune reactions in various clinical contexts. TLTs are closely associated with aging and CKD progression, and the developmental stages of TLTs reflect the severity of renal injury. In this review, we describe the current understanding of fibroblast heterogeneity both under physiological and pathological conditions, with special emphasis on fibroblast contribution to TLT formation in the kidney. Dissecting the heterogeneous characteristics of fibroblasts will provide a promising therapeutic option for fibroblast-related pathological conditions, including TLT formation.

中文翻译：

---

成纤维细胞异质性和肾脏中的三级淋巴组织

成纤维细胞存在于各种器官中，在生理条件下支持组织结构和体内平衡。成纤维细胞的表型改变是多种病理状况发展的基础，包括器官纤维化。单细胞生物学的最新进展表明，成纤维细胞包含具有不同表型的异质亚群，它们以上下文相关的方式对宿主器官产生有益和有害的影响。在肾脏中，常驻成纤维细胞的表型改变会引发慢性肾脏病 (CKD) 的常见病理状况，例如肾性贫血和管周毛细血管丢失。此外，在老化的受损肾脏中，成纤维细胞为三级淋巴组织 (TLT) 提供功能和结构支持，在各种临床环境中作为获得性免疫反应的异位部位。TLTs 与衰老和 CKD 进展密切相关，TLTs 的发育阶段反映了肾损伤的严重程度。在这篇综述中，我们描述了目前对生理和病理条件下成纤维细胞异质性的理解，特别强调成纤维细胞对肾脏 TLT 形成的贡献。剖析成纤维细胞的异质特征将为成纤维细胞相关的病理状况（包括 TLT 形成）提供有希望的治疗选择。我们描述了目前对生理和病理条件下成纤维细胞异质性的理解，特别强调成纤维细胞对肾脏 TLT 形成的贡献。剖析成纤维细胞的异质特征将为成纤维细胞相关的病理状况（包括 TLT 形成）提供有希望的治疗选择。我们描述了目前对生理和病理条件下成纤维细胞异质性的理解，特别强调成纤维细胞对肾脏 TLT 形成的贡献。剖析成纤维细胞的异质特征将为成纤维细胞相关的病理状况（包括 TLT 形成）提供有希望的治疗选择。