Uribe Felipe R, González-Martínez Fabián, Echeverría-Araya Sebastián A, Sepúlveda-Pontigo Alison, Chávez-Villacreses Karissa, Díaz-Bozo Andrés, Méndez-Pérez Isabel, González Valentina P I, Bohmwald Karen, Kalergis Alexis M, Soto Jorge A
Millennium Institute on Immunology and Immunotherapy, Laboratorio de Inmunología Traslacional, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago 8370133, Chile.
Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago 8900000, Chile.
Int J Mol Sci. 2024 Dec 19;25(24):13604. doi: 10.3390/ijms252413604.
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by self-antibody production and widespread inflammation affecting various body tissues. This disease is driven by the breakdown of immune tolerance, which promotes the activation of autoreactive B and T cells. A key feature of SLE is dysregulation in antigen presentation, where antigen-presenting cells (APCs) play a central role in perpetuating immune responses. Dendritic cells (DCs) are highly specialized for antigen presentation among APCs. At the same time, myeloid-derived suppressor cells (MDSCs) can also express MHC-II molecules, although their role in SLE is less understood. Utilizing the SLE model, MRL/MpJ-/J, we determined the presence of different phenotypes of DCs and MDSCs expressing MHC-II in secondary lymphoid organs, along with the gene expression of , and in the spleen. Our study determined that the most abundant population of APCs in secondary lymphoid organs corresponds to cDC CD103CD11b MHC-II throughout SLE development. Additionally, expression increased over time, becoming more preponderant in week 16 in the SLE model, which could indicate that it is a crucial pathway for the development and progression of the pathology. In week 16, we observed a positive correlation between M-MDSC MHC-II and IFN-γ-producing CD4 T cells.
系统性红斑狼疮(SLE)是一种自身免疫性疾病,其特征是产生自身抗体以及影响身体各个组织的广泛炎症。这种疾病是由免疫耐受的破坏驱动的,免疫耐受的破坏促进了自身反应性B细胞和T细胞的激活。SLE的一个关键特征是抗原呈递失调,其中抗原呈递细胞(APC)在维持免疫反应中起核心作用。在APC中,树突状细胞(DC)高度专门化用于抗原呈递。同时,髓系来源的抑制细胞(MDSC)也可以表达MHC-II分子,尽管它们在SLE中的作用尚不太清楚。利用SLE模型MRL/MpJ-/J,我们确定了在二级淋巴器官中表达MHC-II的不同表型的DC和MDSC的存在,以及脾脏中 、 和 的基因表达。我们的研究确定,在整个SLE发展过程中,二级淋巴器官中最丰富的APC群体对应于cDC CD103CD11b MHC-II。此外, 表达随时间增加,在SLE模型的第16周变得更加占优势,这可能表明它是该病理发展和进展的关键途径。在第16周,我们观察到M-MDSC MHC-II与产生IFN-γ的CD4 T细胞之间呈正相关。