Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan; Department of Osteoimmunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo, 113-8549, Japan; JST, Precursory Research for Embryonic Science and Technology (PRESTO), Yushima 1-5-45, Bunkyo-ku, Tokyo, 113-8549, Japan; Japan Agency for Medical Research and development, Core Research for Evolutional Science and Technology (AMED-CREST) Yushima 1-5-45, Bunkyo-ku, Tokyo, 113-8549, Japan.
Immunity. 2016 Jun 21;44(6):1434-43. doi: 10.1016/j.immuni.2016.05.012. Epub 2016 Jun 14.
Sepsis is a host inflammatory response to severe infection associated with high mortality that is caused by lymphopenia-associated immunodeficiency. However, it is unknown how lymphopenia persists after the accelerated lymphocyte apoptosis subsides. Here we show that sepsis rapidly ablated osteoblasts, which reduced the number of common lymphoid progenitors (CLPs). Osteoblast ablation or inducible deletion of interleukin-7 (IL-7) in osteoblasts recapitulated the lymphopenic phenotype together with a lower CLP number without affecting hematopoietic stem cells (HSCs). Pharmacological activation of osteoblasts improved sepsis-induced lymphopenia. This study demonstrates a reciprocal interaction between the immune and bone systems, in which acute inflammation induces a defect in bone cells resulting in lymphopenia-associated immunodeficiency, indicating that bone cells comprise a therapeutic target in certain life-threatening immune reactions.
脓毒症是一种宿主炎症反应，由严重感染引起，与死亡率高相关，其由淋巴细胞减少相关免疫缺陷引起。然而，目前尚不清楚淋巴细胞减少在加速淋巴细胞凋亡消退后如何持续存在。在这里，我们发现脓毒症迅速消融成骨细胞，导致共同淋巴祖细胞（CLP）数量减少。成骨细胞消融或成骨细胞中白细胞介素 7（IL-7）的诱导性缺失，在不影响造血干细胞（HSCs）的情况下，共同再现了淋巴细胞减少表型和较低的 CLP 数量。成骨细胞的药理学激活改善了脓毒症引起的淋巴细胞减少。这项研究证明了免疫和骨骼系统之间的相互作用，其中急性炎症导致骨细胞缺陷，导致与淋巴细胞减少相关的免疫缺陷，表明骨细胞是某些危及生命的免疫反应的治疗靶点。
