Robert Marie, Miossec Pierre
Département d'immunologie clinique et de rhumatologie, Unité immunogénomique et inflammation, Hôpital Edouard Herriot, Hospices Civils de Lyon, 5 Place d'Arsonval, 69437 Lyon, France.
Biol Aujourdhui. 2024;218(1-2):33-39. doi: 10.1051/jbio/2024004. Epub 2024 Jul 15.
Interleukin (IL)-17A and then IL-17F have been discovered through their roles in chronic inflammatory diseases. These cytokines share 50% of sequence homology and bind to the same receptor made of the IL-17RA et IL-17RC chains. While they have rather similar pro-inflammatory effects, slight differences exist depending on the cell type considered or whether there is TNF or not. Indeed, there is a synergistic effect of TNF and IL-17A or IL-17F on many cell types. In addition, the interactions between immune and stromal cells also modulate their effects which vary according to stromal cell subtype. The identification of IL-17A and IL-17F roles in inflammatory diseases, as psoriasis, has led to the development of inhibitors of those cytokines. Anti-IL-17A, then anti-IL-17A/F and now anti-IL-17RA have been approved for different diseases and are particularly efficient in psoriasis. Their use is expending to other diseases like psoriatic arthritis and spondyloarthritis. Last, the recent understanding of the importance of stromal cells during chronic inflammation explains the relative inefficacy of such inhibitors in some other diseases.
白细胞介素(IL)-17A随后是IL-17F,是通过它们在慢性炎症性疾病中的作用而被发现的。这些细胞因子具有50%的序列同源性,并与由IL-17RA和IL-17RC链组成的相同受体结合。虽然它们具有相当相似的促炎作用,但根据所考虑的细胞类型或是否存在肿瘤坏死因子(TNF),仍存在细微差异。事实上,TNF与IL-17A或IL-17F在许多细胞类型上具有协同作用。此外,免疫细胞与基质细胞之间的相互作用也会调节它们的作用,其作用会因基质细胞亚型而异。IL-17A和IL-17F在炎症性疾病(如银屑病)中的作用被确定后,促使了这些细胞因子抑制剂的研发。抗IL-17A、随后的抗IL-17A/F以及现在的抗IL-17RA已被批准用于不同疾病,在银屑病中尤为有效。它们的应用正在扩展到其他疾病,如银屑病关节炎和脊柱关节炎。最后,最近对基质细胞在慢性炎症中重要性的认识解释了此类抑制剂在其他一些疾病中相对无效的原因。