イシズ　アヤコ   Ishizu Ayako   石津　綾子    所属   医学部 医学科    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Bacterial c-di-GMP affects hematopoietic stem/progenitors and their niches through STING.
掲載誌名	正式名：Cell reports 略　 称：Cell Rep ISSNコード：22111247
掲載区分	国外
巻・号・頁	11(1),pp.71-84
著者・共著者	Kobayashi Hiroshi, Kobayashi Chiharu I, Nakamura-Ishizu Ayako, Karigane Daiki, Haeno Hiroshi, Yamamoto Kimiyo N, Sato Taku, Ohteki Toshiaki, Hayakawa Yoshihiro, Barber Glen N, Kurokawa Mineo, Suda Toshio, Takubo Keiyo
発行年月	2015/04
概要	Upon systemic bacterial infection, hematopoietic stem and progenitor cells (HSPCs) migrate to the periphery in order to supply a sufficient number of immune cells. Although pathogen-associated molecular patterns reportedly mediate HSPC activation, how HSPCs detect pathogen invasion in vivo remains elusive. Bacteria use the second messenger bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) for a variety of activities. Here, we report that c-di-GMP comprehensively regulated both HSPCs and their niche cells through an innate immune sensor, STING, thereby inducing entry into the cell cycle and mobilization of HSPCs while decreasing the number and repopulation capacity of long-term hematopoietic stem cells. Furthermore, we show that type I interferon acted as a downstream target of c-di-GMP to inhibit HSPC expansion in the spleen, while transforming growth factor-β was required for c-di-GMP-dependent splenic HSPC expansion. Our results define machinery underlying the dynamic regulation of HSPCs and their niches during bacterial infection through c-di-GMP/STING signaling.
DOI	10.1016/j.celrep.2015.02.066
PMID	25843711