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Blood, Published online August 6, 2019 | doi: https://doi.org/10.1182/blood.2019000495 Bone marrow CX3CR1+ mononuclear cells relay a systemic microbiota signal to control hematopoietic progenitors in mice

Seungwon Lee,^1,* Hyekang Kim,^1,* Gihoon You,¹ Young-Min Kim,² Seunghun Lee,³ Viet Hoan Le,¹ Ohseop Kwon,¹ Sin-Hyeog Im,^1,2,4 You-Me Kim,^1,2 Kwang Soon Kim,^1,4 Young Chul Sung,^1,2 Ki Hean Kim,^1,3 Charles D. Surh,^1,2,4,5 Yunji Park,¹ and Seung-Woo Lee^1,2

¹Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea; ²Department of Life Sciences, POSTECH, Pohang, Republic of Korea; ³Department of Mechanical Engineering, POSTECH, Pohang, Republic of Korea; ⁴Academy of Immunology and Microbiology, Institute for Basic Science, Pohang, Republic of Korea; ⁵Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.

^*S.L. and H.K. contributed equally to this study.

Correspondence: Seung-Woo Lee, Division of Integrative Biosciences & Biotechnology, Department
of Life Sciences, POSTECH, 77 Cheongam-Ro. Nam-Gu. Pohang. Gyeongbuk. Republic of Korea
37673; and Yunji Park, Division of Integrative Biosciences & Biotechnology, POSTECH, 77 Cheongam-Ro. Nam-Gu. Pohang. Gyeongbuk. Republic of Korea 37673

Abstract

The microbiota regulate hematopoiesis in the bone marrow (BM); however, the detailed mechanisms remain largely unknown. In this study, we explored how microbiota-derived molecules (MDMs) were transferred to the BM and sensed by the local immune cells to control hematopoiesis under steady-state conditions. We reveal that MDMs, including bacterial DNA (bDNA), reach the BM via systemic blood circulation and are captured by CX3CR1+ mononuclear cells (MNCs). CX3CR1+ MNCs sense MDMs via endolysosomal toll-like receptors (TLRs) to produce inflammatory cytokines, which control the basal expansion of hematopoietic progenitors, but not HSCs, and their differentiation potential toward myeloid lineages. CX3CR1+ MNCs co-locate with hematopoietic progenitors at the perivascular region, and the depletion of CX3CR1+ MNCs impedes bDNA influx into the BM. Moreover, the abrogation of TLR pathways in CX3CR1+ MNCs abolished the microbiota effect on hematopoiesis. These studies demonstrate that systemic MDMs control BM hematopoiesis by producing CX3CR1+ MNC-mediated cytokines in the steady-state.

논문정보

TOP52019년 선정

형식Research article
게재일2019년 08월 (BRIC 등록일 2019-08-20)
연구진국내(교신)+국외 연구진
분야 생명과학 > 면역학

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