Department of Infection and Immunity, Luxembourg Institute of Health, 29 rue Henri Koch, L-4354 Esch-sur Alzette, Luxembourg.
Cells. 2020 Apr 2;9(4):865. doi: 10.3390/cells9040865.
The neurotrophic factors are well known for their implication in the growth and the survival of the central, sensory, enteric and parasympathetic nervous systems. Due to these properties, neurturin (NRTN) and Glial cell-derived neurotrophic factor (GDNF), which belong to the GDNF family ligands (GFLs), have been assessed in clinical trials as a treatment for neurodegenerative diseases like Parkinson's disease. In addition, studies in favor of a functional role for GFLs outside the nervous system are accumulating. Thus, GFLs are present in several peripheral tissues, including digestive, respiratory, hematopoietic and urogenital systems, heart, blood, muscles and skin. More precisely, recent data have highlighted that different types of immune and epithelial cells (macrophages, T cells, such as, for example, mucosal-associated invariant T (MAIT) cells, innate lymphoid cells (ILC) 3, dendritic cells, mast cells, monocytes, bronchial epithelial cells, keratinocytes) have the capacity to release GFLs and express their receptors, leading to the participation in the repair of epithelial barrier damage after inflammation. Some of these mechanisms pass on to ILCs to produce cytokines (such as IL-22) that can impact gut microbiota. In addition, there are indications that NRTN could be used in the treatment of inflammatory airway diseases and it prevents the development of hyperglycemia in the diabetic rat model. On the other hand, it is suspected that the dysregulation of GFLs produces oncogenic effects. This review proposes the discussion of the biological understanding and the potential new opportunities of the GFLs, in the perspective of developing new treatments within a broad range of human diseases.
神经营养因子因其对中枢神经系统、感觉神经系统、肠神经系统和副交感神经系统的生长和存活的影响而广为人知。由于这些特性，神经生长因子（NRTN）和胶质细胞源性神经营养因子（GDNF），属于 GDNF 家族配体（GFLs），已在临床试验中被评估为治疗帕金森病等神经退行性疾病的方法。此外，越来越多的研究支持 GFLs 在神经系统之外具有功能作用。因此，GFLs 存在于多个外周组织中，包括消化、呼吸、造血和泌尿生殖系统、心脏、血液、肌肉和皮肤。更确切地说，最近的数据强调了不同类型的免疫和上皮细胞（巨噬细胞、T 细胞，例如黏膜相关不变 T（MAIT）细胞、先天淋巴细胞（ILC）3、树突状细胞、肥大细胞、单核细胞、支气管上皮细胞、角质形成细胞）具有释放 GFLs 和表达其受体的能力，从而参与炎症后上皮屏障损伤的修复。其中一些机制传递给 ILCs 以产生细胞因子（如 IL-22），从而影响肠道微生物群。此外，有迹象表明 NRTN 可用于治疗炎症性气道疾病，并可预防糖尿病大鼠模型中高血糖的发展。另一方面，人们怀疑 GFLs 的失调会产生致癌作用。本综述提出了从生物角度理解 GFLs 的作用，并探讨了它们在广泛的人类疾病中开发新治疗方法的潜在新机会。
