Department of Immunology, Weizmann Institute of Science, 76100 Rehovot, Israel.
Department of Chronic Inflammation and Cancer, German Cancer Research Center, 69120 Heidelberg, Germany.
Proc Natl Acad Sci U S A. 2019 Aug 13;116(33):16489-16496. doi: 10.1073/pnas.1900079116. Epub 2019 Jul 25.
SLAMF9 belongs to the conserved lymphocytic activation molecule family (SLAMF). Unlike other SLAMs, which have been extensively studied, the role of SLAMF9 in the immune system remained mostly unexplored. By generating CRISPR/Cas9 SLAMF9 knockout mice, we analyzed the role of this receptor in plasmacytoid dendritic cells (pDCs), which preferentially express the SLAMF9 transcript and protein. These cells display a unique capacity to produce type I IFN and bridge between innate and adaptive immune response. Analysis of pDCs in SLAMF9 mice revealed an increase of immature pDCs in the bone marrow and enhanced accumulation of pDCs in the lymph nodes. In the periphery, SLAMF9 deficiency resulted in lower levels of the transcription factor SpiB, elevation of pDC survival, and attenuated IFN-α and TNF-α production. To define the role of SLAMF9 during inflammation, pDCs lacking SLAMF9 were followed during induced experimental autoimmune encephalomyelitis. SLAMF9 mice demonstrated attenuated disease and delayed onset, accompanied by a prominent increase of immature pDCs in the lymph node, with a reduced costimulatory potential and enhanced infiltration of pDCs into the central nervous system. These results suggest the crucial role of SLAMF9 in pDC differentiation, homeostasis, and function in the steady state and during experimental autoimmune encephalomyelitis.
SLAMF9 属于保守的淋巴细胞激活分子家族（SLAMF）。与其他 SLAMs 不同，后者的研究已经很广泛，而 SLAMF9 在免疫系统中的作用在很大程度上仍未得到探索。通过生成 CRISPR/Cas9 SLAMF9 敲除小鼠，我们分析了这种受体在浆细胞样树突状细胞（pDCs）中的作用，pDCs 优先表达 SLAMF9 转录本和蛋白。这些细胞显示出独特的产生 I 型 IFN 的能力，并在先天免疫和适应性免疫反应之间架起桥梁。在 SLAMF9 小鼠中对 pDCs 的分析表明，骨髓中不成熟的 pDCs 增加，淋巴结中 pDCs 的积累增强。在外周，SLAMF9 缺乏导致转录因子 SpiB 水平降低、pDC 存活增加以及 IFN-α 和 TNF-α 产生减少。为了确定 SLAMF9 在炎症过程中的作用，在诱导的实验性自身免疫性脑脊髓炎期间跟踪缺乏 SLAMF9 的 pDCs。SLAMF9 小鼠表现出疾病减轻和发病延迟，伴有淋巴结中不成熟的 pDCs 明显增加，共刺激潜力降低，pDCs 浸润到中枢神经系统增加。这些结果表明 SLAMF9 在 pDC 分化、稳态以及在实验性自身免疫性脑脊髓炎中的功能中起着至关重要的作用。
