Briseño Carlos G, Haldar Malay, Kretzer Nicole M, Wu Xiaodi, Theisen Derek J, Kc Wumesh, Durai Vivek, Grajales-Reyes Gary E, Iwata Arifumi, Bagadia Prachi, Murphy Theresa L, Murphy Kenneth M
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA.
Department of Pathology and Laboratory Medicine, Perelman School of Medicine and Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell Rep. 2016 Jun 14;15(11):2462-74. doi: 10.1016/j.celrep.2016.05.025. Epub 2016 Jun 2.
Both classical DCs (cDCs) and monocyte-derived DCs (Mo-DCs) are capable of cross-priming CD8(+) T cells in response to cell-associated antigens. We found that Ly-6C(hi)TREML4(-) monocytes can differentiate into Zbtb46(+) Mo-DCs in response to granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) but that Ly-6C(hi)TREML4(+) monocytes were committed to differentiate into Ly-6C(lo)TREML4(+) monocytes. Differentiation of Zbtb46(+) Mo-DCs capable of efficient cross-priming required both GM-CSF and IL-4 and was accompanied by the induction of Batf3 and Irf4. However, monocytes require IRF4, but not BATF3, to differentiate into Zbtb46(+) Mo-DCs capable of cross-priming CD8(+) T cells. Instead, Irf4(-/-) monocytes differentiate into macrophages in response to GM-CSF and IL-4. Thus, cDCs and Mo-DCs require distinct transcriptional programs of differentiation in acquiring the capacity to prime CD8(+) T cells. These differences may be of consideration in the use of therapeutic DC vaccines based on Mo-DCs.
经典树突状细胞（cDCs）和单核细胞衍生的树突状细胞（Mo-DCs）都能够针对细胞相关抗原交叉启动CD8(+) T细胞。我们发现，Ly-6C(hi)TREML4(-)单核细胞在粒细胞-巨噬细胞集落刺激因子（GM-CSF）和白细胞介素-4（IL-4）的作用下可分化为Zbtb46(+) Mo-DCs，但Ly-6C(hi)TREML4(+)单核细胞则会定向分化为Ly-6C(lo)TREML4(+)单核细胞。能够有效交叉启动的Zbtb46(+) Mo-DCs的分化需要GM-CSF和IL-4两者，并伴随着Batf3和Irf4的诱导。然而，单核细胞分化为能够交叉启动CD8(+) T细胞的Zbtb46(+) Mo-DCs需要IRF4，但不需要BATF3。相反，Irf4(-/-)单核细胞在GM-CSF和IL-4的作用下分化为巨噬细胞。因此，cDCs和Mo-DCs在获得启动CD8(+) T细胞的能力时需要不同的转录分化程序。在使用基于Mo-DCs的治疗性树突状细胞疫苗时，这些差异可能需要考虑。
