Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Immunology. 2011 Jan;132(1):87-95. doi: 10.1111/j.1365-2567.2010.03342.x. Epub 2010 Aug 25.
Systemic lupus erythematosus (SLE) is an autoimmune disease that involves dysregulation of B and T cells. A tolerogenic peptide, designated hCDR1, ameliorates disease manifestations in SLE-afflicted mice. In the present study, the effect of treatment with hCDR1 on the CD74/macrophage migration inhibitory factor (MIF) pathway was studied. We report here that B lymphocytes from SLE-afflicted mice express relatively elevated levels of CD74, compared with B cells from healthy mice. CD74 is a receptor found in complex with CD44, and it binds the pro-inflammatory cytokine MIF. The latter components were also up-regulated in B cells from the diseased mice, and treatment with hCDR1 resulted in their down-regulation and in reduced B-cell survival. Furthermore, up-regulation of CD74 and CD44 expression was detected in brain hippocampi and kidneys, two target organs in SLE. Treatment with hCDR1 diminished the expression of those molecules to the levels determined for young healthy mice. These results suggest that the CD74/MIF pathway plays an important role in lupus pathology.
系统性红斑狼疮 (SLE) 是一种自身免疫性疾病，涉及 B 和 T 细胞的失调。一种耐受性肽，称为 hCDR1，可改善 SLE 小鼠的疾病表现。在本研究中，研究了 hCDR1 治疗对 CD74/巨噬细胞迁移抑制因子 (MIF) 途径的影响。我们在这里报告，与来自健康小鼠的 B 细胞相比，来自 SLE 小鼠的 B 淋巴细胞表达相对升高的 CD74。CD74 是一种与 CD44 结合的受体，它结合促炎细胞因子 MIF。后两种成分在患病小鼠的 B 细胞中也上调，hCDR1 治疗导致其下调和 B 细胞存活减少。此外，在 SLE 的两个靶器官——大脑海马体和肾脏中，检测到 CD74 和 CD44 表达上调。hCDR1 治疗将这些分子的表达降低到年轻健康小鼠确定的水平。这些结果表明 CD74/MIF 途径在狼疮病理中起重要作用。
