Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan;
J Immunol. 2014 Mar 1;192(5):2271-9. doi: 10.4049/jimmunol.1301914. Epub 2014 Jan 31.
IRF4 is a transcription factor from the IRF factor family that plays pivotal roles in the differentiation and function of T and B lymphocytes. Although IRF4 is also expressed in dendritic cells (DCs) and macrophages, its roles in these cells in vivo are not clearly understood. In this study, conditional knockout mice that lack IRF4 in DCs or macrophages were generated and infected with Leishmania major. Mice lacking DC expression of IRF4 showed reduced footpad swelling compared with C57BL/6 mice, whereas those lacking IRF4 in macrophages did not. Mice with IRF4-deficient DCs also showed reduced parasite burden, and their CD4(+) T cells produced higher levels of IFN-γ in response to L. major Ag. In the draining lymph nodes, the proportion of activated CD4(+) T cells in these mice was similar to that in the control, but the proportion of IFN-γ-producing cells was increased, suggesting a Th1 bias in the immune response. Moreover, the numbers of migrating Langerhans cells and other migratory DCs in the draining lymph nodes were reduced both before and postinfection in mice with IRF4 defects in DCs, but higher levels of IL-12 were observed in IRF4-deficient DCs. These results imply that IRF4 expression in DCs inhibits their ability to produce IL-12 while promoting their migratory behavior, thus regulating CD4(+) T cell responses against local infection with L. major.
IRF4 是干扰素调节因子（IRF）家族中的一种转录因子，在 T 和 B 淋巴细胞的分化和功能中发挥关键作用。尽管 IRF4 也在树突状细胞（DC）和巨噬细胞中表达，但它在这些细胞中的作用在体内尚未得到明确的了解。在这项研究中，生成了条件性敲除 DC 或巨噬细胞中 IRF4 的小鼠，并使其感染了嗜酸性利什曼原虫。与 C57BL/6 小鼠相比，缺乏 DC 表达 IRF4 的小鼠的足垫肿胀程度降低，而缺乏巨噬细胞中 IRF4 的小鼠则没有。缺乏 IRF4 的 DC 的小鼠寄生虫负担也降低，其 CD4(+) T 细胞对 L. major Ag 的反应产生更高水平的 IFN-γ。在引流淋巴结中，这些小鼠中激活的 CD4(+) T 细胞的比例与对照相似，但产生 IFN-γ 的细胞的比例增加，表明免疫反应偏向 Th1。此外，在缺乏 DC 中 IRF4 的小鼠中，在感染前后，引流淋巴结中的迁移朗格汉斯细胞和其他迁移 DC 的数量均减少，但在缺乏 IRF4 的 DC 中观察到更高水平的 IL-12。这些结果表明，DC 中 IRF4 的表达抑制了它们产生 IL-12 的能力，同时促进了它们的迁移行为，从而调节了针对局部感染嗜酸性利什曼原虫的 CD4(+) T 细胞反应。
