Sepsis-Induced Osteoblast Ablation Causes Immunodeficiency

• Published in: Immunity (Cambridge, Mass.) Mass.), 2016-06, Vol.44 (6), p.1434-1443
• Main Authors: Terashima, Asuka, Okamoto, Kazuo, Nakashima, Tomoki, Akira, Shizuo, Ikuta, Koichi, Takayanagi, Hiroshi
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; B-Lymphocytes - physiology; Bone marrow; Cells, Cultured; Cytokines - metabolism; Grants; Homeostasis; Immunoglobulins; Immunologic Deficiency Syndromes - immunology; Inflammation; Interleukin-7 - genetics; Interleukin-7 - metabolism; Lymphocyte Depletion; Lymphoid Progenitor Cells - physiology; Lymphopenia; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteoblasts - physiology; R&D; Research & development; Rodents; Sepsis; Sepsis - immunology; Studies; T-Lymphocytes - physiology
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2016.05.012

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. [Display omitted] •Sepsis reduces the number of osteoblasts and common lymphoid progenitors•Inducible osteoblast ablation leads to T and B lymphopenia•Osteoblast-derived IL-7 is required for development of common lymphoid progenitors•Sepsis-induced immunodeficiency is ameliorated by osteoblast stimulation Much has been done on the identification of HSC niche, but the role of osteoblasts in hematopoiesis is unknown in acute immune responses. Takayanagi and colleagues show that sepsis reduces the osteoblast number, which induces lymphopenia through IL-7 downregulation, demonstrating a reciprocal interaction between the immune and bone systems.