Rafei Moutih, Galipeau Jacques
Institute for Research in Immunology and Cancer, University of Montreal, Montreal, Quebec Canada.
Crit Rev Immunol. 2010;30(5):449-61. doi: 10.1615/critrevimmunol.v30.i5.40.
Autoimmune diseases represent one of the most challenging clinical entities with unmet medical needs, so the continued development of novel therapeutics is well justified. Most autoimmune diseases are marked by the infiltration of lymphomyeloid cells in target tissues, leading to inflammation and tissue damage. This process is guided by chemokines that act as signaling bridges amidst a complex network of immune cells. For example, monocytes are believed to be the primary cell type responsible for pathology initiation and tissue damage, while T lymphocytes are thought to orchestrate the process by secreting more cytokines/chemokines to amplify leukocyte homing. Many studies have addressed the molecular basis of monocyte recruitment in different autoimmune diseases, and the conclusions pointed to a major role played by monocyte chemoattractant protein 1 (MCP-1), also known as CC chemokine ligand 2 (CCL2), and its cell-surface receptor, CC chemokine receptor (CCR) 2. These findings suggest that by interfering with CCL2 or its receptor, it is possible to inhibit the progression of CCR2-dependent diseases. Therefore, future therapy design targeting a maladapted immune response could target chemokine receptors starting with the CCL2-CCR2 axis.
自身免疫性疾病是最具挑战性的临床病症之一，存在未满足的医疗需求，因此新型疗法的持续研发具有充分的合理性。大多数自身免疫性疾病的特征是靶组织中淋巴细胞和髓样细胞浸润，导致炎症和组织损伤。这一过程由趋化因子引导，趋化因子在复杂的免疫细胞网络中充当信号桥梁。例如，单核细胞被认为是引发病理和组织损伤的主要细胞类型，而T淋巴细胞则被认为通过分泌更多细胞因子/趋化因子来放大白细胞归巢从而协调这一过程。许多研究探讨了不同自身免疫性疾病中单核细胞募集的分子基础，结论指出单核细胞趋化蛋白1（MCP-1，也称为CC趋化因子配体2 （CCL2））及其细胞表面受体CC趋化因子受体（CCR）2发挥了主要作用。这些发现表明，通过干扰CCL2或其受体，有可能抑制CCR2依赖性疾病的进展。因此，未来针对适应性不良免疫反应的治疗设计可以从CCL2-CCR2轴开始靶向趋化因子受体。
