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Immunity. 2016 Jun 21;44(6):1434-43. doi: 10.1016/j.immuni.2016.05.012. Epub 2016 Jun 14.

Sepsis-Induced Osteoblast Ablation Causes Immunodeficiency.

Author information

1
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.
2
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.
3
Laboratory of Host Defense, WPI Immunology Frontier Research Center (IFReC), Osaka University, Yamada-oka 3-1, Suita, Osaka 565-0871, Japan.
4
Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
5
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. Electronic address: takayana@m.u-tokyo.ac.jp.

Abstract

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.

PMID:
27317262
DOI:
10.1016/j.immuni.2016.05.012
[Indexed for MEDLINE]
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