Department of Immunology, Zunyi Medical University, Zunyi, China.
Department of Respiratory Medicine, The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, China.
Autoimmunity. 2023 Dec;56(1):2259127. doi: 10.1080/08916934.2023.2259127. Epub 2023 Sep 23.
The Hedgehog (Hh) family is a prototypical morphogen involved in embryonic patterning, multi-lineage differentiation, self-renewal, morphogenesis, and regeneration. There are studies that have demonstrated that the Hh signaling pathway differentiates developing T cells into MHC-restricted self-antigen tolerant T cells in a concentration-dependent manner in the thymus. Whereas Hh signaling pathway is not required in the differentiation of B cells but is indispensable in maintaining the regeneration of hematopoietic stem cells (HSCs) and the viability of germinal centers (GCs) B cells. The Hh signaling pathway exerts both positive and negative effects on immune responses, which involves activating human peripheral CD4 T cells, regulating the accumulation of natural killer T (NKT) cells, recruiting and activating macrophages, increasing CD4Foxp3 regulatory T cells in the inflammation sites to sustain homeostasis. Hedgehog signaling is involved in the patterning of the embryo, as well as homeostasis of adult tissues. Therefore, this review aims to highlight evidence for Hh signaling in the differentiation, function of immune cells and autoimmune disease. Targeting Hh signaling promises to be a novel, alternative or adjunct approach to treating tumors and autoimmune diseases.
刺猬 (Hh) 家族是一种典型的形态发生素，参与胚胎模式形成、多谱系分化、自我更新、形态发生和再生。有研究表明，Hh 信号通路在胸腺中以浓度依赖性的方式将发育中的 T 细胞分化为 MHC 限制性自身抗原耐受的 T 细胞。虽然 Hh 信号通路在 B 细胞的分化中不是必需的，但对于维持造血干细胞 (HSCs) 的再生和生发中心 (GC) B 细胞的存活是必不可少的。Hh 信号通路对免疫反应既有正作用也有负作用，它涉及激活人外周 CD4 T 细胞、调节自然杀伤 T (NKT) 细胞的积累、招募和激活巨噬细胞、增加炎症部位的 CD4Foxp3 调节性 T 细胞以维持内稳态。Hedgehog 信号通路参与胚胎的模式形成以及成体组织的稳态。因此，本综述旨在强调 Hh 信号通路在免疫细胞分化、功能和自身免疫性疾病中的作用。靶向 Hh 信号通路有望成为治疗肿瘤和自身免疫性疾病的一种新的、替代的或辅助的方法。
