LECT2 drives haematopoietic stem cell expansion and mobilization via regulating the macrophages and osteolineage cells.
Haematopoietic stem cells (HSCs) can differentiate into cells of all lineages in the blood. However, the mechanisms by which cytokines in the blood affect HSC homeostasis remain largely unknown. Here we show that leukocyte cell-derived chemotaxin 2 (LECT2), a multifunctional cytokine, induces HSC expansion and mobilization. Recombinant LECT2 administration results in HSC expansion in the bone marrow and mobilization to the blood via CD209a. The effect of LECT2 on HSCs is reduced after specific depletion of macrophages or reduction of osteolineage cells. LECT2 treatment reduces the tumour necrosis factor (TNF) expression in macrophages and osteolineage cells. In TNF knockout mice, the effect of LECT2 on HSCs is reduced. Moreover, LECT2 induces HSC mobilization in irradiated mice, while granulocyte colony-stimulating factor does not. Our results illustrate that LECT2 is an extramedullar cytokine that contributes to HSC homeostasis and may be useful to induce HSC mobilization.
Laboratory of Biochemistry and Molecular Biology, Department of Marine and Life Sciences, Ningbo University, Ningbo 315211, China.
Xin-Jiang
0000-0002-7796-4401
XJ
Lu
Laboratory of Biochemistry and Molecular Biology, Department of Marine and Life Sciences, Ningbo University, Ningbo 315211, China.
Qiang
Q
Chen
Laboratory of Biochemistry and Molecular Biology, Department of Marine and Life Sciences, Ningbo University, Ningbo 315211, China.
Ye-Jing
YJ
Rong
Laboratory of Biochemistry and Molecular Biology, Department of Marine and Life Sciences, Ningbo University, Ningbo 315211, China.
Guan-Jun
GJ
Yang
Laboratory of Biochemistry and Molecular Biology, Department of Marine and Life Sciences, Ningbo University, Ningbo 315211, China.
Chang-Hong
CH
Li
Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Ning-Yi
NY
Xu
Department of Gastroenterology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
Chao-Hui
CH
Yu
Department of Allergy and Clinical Immunology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
Hui-Ying
HY
Wang
Clinical Research Center, Ningbo No. 2 Hospital, Ningbo 315010, China.
Shun
S
Zhang
Laboratory of Biochemistry and Molecular Biology, Department of Marine and Life Sciences, Ningbo University, Ningbo 315211, China.
Yu-Hong
YH
Shi
Laboratory of Biochemistry and Molecular Biology, Department of Marine and Life Sciences, Ningbo University, Ningbo 315211, China.
Jiong
J
Chen
D000818:Animals; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D019070:Cell Lineage / Q000502:physiology*; D003412:Cricetulus; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D016179:Granulocyte Colony-Stimulating Factor; D036341:Intercellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C491213:Lect2 protein, mouse