Hagnerud Sven, Manna Partha Pratim, Cella Marina, Stenberg Asa, Frazier William A, Colonna Marco, Oldenborg Per-Arne
Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University, SE-901 87 Umeå, Sweden.
J Immunol. 2006 May 15;176(10):5772-8. doi: 10.4049/jimmunol.176.10.5772.
CD47 is a ubiquitously expressed cell surface glycoprotein that associates with integrins and regulates chemotaxis, migration, and activation of leukocytes. CD47 is also a ligand for signal regulatory protein alpha, a cell surface receptor expressed on monocytes, macrophages, granulocytes, and dendritic cell (DC) subsets that regulates cell activation, adhesion, and migration. Although the function of CD47 in macrophages and granulocytes has been studied in detail, little is known about the role of CD47 in DC biology in vivo. In this study we demonstrate that CD47(-/-) mice exhibit a selective reduction of splenic CD11c(high)CD11b(high)CD8alpha(-)CD4(+) DCs. These DCs correspond to marginal zone DCs and express signal regulatory protein alpha, possibly explaining their selective deficiency in CD47(-/-) mice. Deficiency of marginal zone DCs resulted in impairment of IgG responses to corpusculate T cell-independent Ags. Although epidermal DCs were present in normal numbers in CD47(-/-) mice, their migration to draining lymph nodes in response to contact sensitization was impaired, while their maturation was intact. In vitro, CD47(-/-) mature DCs showed normal CCR7 expression but impaired migration to CCL-19, whereas immature DC response to CCL-5 was only slightly impaired. These results demonstrate a fundamental role of CD47 in DC migration in vivo and in vitro and in the function of marginal zone DCs.
CD47是一种广泛表达的细胞表面糖蛋白，它与整合素相关联并调节白细胞的趋化性、迁移和激活。CD47也是信号调节蛋白α的配体，信号调节蛋白α是一种在单核细胞、巨噬细胞、粒细胞和树突状细胞（DC）亚群上表达的细胞表面受体，可调节细胞激活、黏附和迁移。尽管已对CD47在巨噬细胞和粒细胞中的功能进行了详细研究，但对CD47在体内DC生物学中的作用却知之甚少。在本研究中，我们证明CD47基因敲除小鼠脾脏中CD11c（高）CD11b（高）CD8α（-）CD4（+）DC选择性减少。这些DC对应于边缘区DC并表达信号调节蛋白α，这可能解释了它们在CD47基因敲除小鼠中的选择性缺陷。边缘区DC的缺乏导致对颗粒性T细胞非依赖性抗原的IgG反应受损。尽管CD47基因敲除小鼠的表皮DC数量正常，但其对接触致敏的迁移至引流淋巴结的能力受损，而其成熟过程完好无损。在体外，CD47基因敲除的成熟DC显示正常的CCR7表达，但迁移至CCL-19的能力受损，而未成熟DC对CCL-5的反应仅略有受损。这些结果证明了CD47在体内和体外DC迁移以及边缘区DC功能中的重要作用。
