Banchereau Jacques, Pascual Virginia
Baylor Institute for Immmunology Research, 3434 Live Oak, Dallas, Texas 75204, USA.
Immunity. 2006 Sep;25(3):383-92. doi: 10.1016/j.immuni.2006.08.010.
Different genetic alterations may lead to type I interferon (IFN) overproduction in human systemic lupus erythematosus (SLE). The increased bioavailability of type I IFN contributes to peripheral tolerance breakdown through the activation of immature myeloid dendritic cells (mDCs). IFN-matured mDCs activate autoreactive T cells. These cells, together with plasmacytoid DCs, help expand autoreactive B cells. IFN-matured DCs also activate cytotoxic CD8+ T cells, possibly increasing apoptotic cell availability. The capture of apoptotic cells by mDCs and of nucleic acid-containing immune complexes by plasmacytoid DCs and B cells amplifies the autoimmune reaction leading to disease manifestations. Genetic alterations in lineages other than B cells might explain other autoimmune syndromes where type I IFNs appear to be involved.
不同的基因改变可能导致人类系统性红斑狼疮（SLE）中I型干扰素（IFN）的过度产生。I型干扰素生物利用度的增加通过激活未成熟髓样树突状细胞（mDC）导致外周耐受破坏。IFN成熟的mDC激活自身反应性T细胞。这些细胞与浆细胞样DC一起，有助于扩增自身反应性B细胞。IFN成熟的DC还激活细胞毒性CD8+T细胞，可能增加凋亡细胞的可用性。mDC对凋亡细胞的捕获以及浆细胞样DC和B细胞对含核酸免疫复合物的捕获会放大自身免疫反应，导致疾病表现。B细胞以外谱系的基因改变可能解释其他似乎涉及I型干扰素的自身免疫综合征。
