Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

ACC 2024 Congress

Catch up on all the top stories and latest evidence in cardiology research with our ACC 2024 Congress hub page.
ADVANCED SEARCH
Log in
Top
International Journal of Hematology
Published in: International Journal of Hematology 1/2017

01-07-2017 | Progress in Hematology

Impact of inflammation on early hematopoiesis and the microenvironment

Authors: Hitoshi Takizawa, Markus G. Manz

Published in: International Journal of Hematology | Issue 1/2017

Login to get access

Abstract

Steady-state hematopoiesis is maintained by slowly dividing, self-renewing hematopoietic stem cells (HSCs) and their offspring, lineage-specified downstream progenitors in bone marrow (BM). It was previously thought that hematopoietic stresses such as infection or other inflammatory stimuli, are mostly recognized by terminally differentiated immune cells, i.e., front-line defenders at the local site of reaction, and that they produce factors that directly act on hematopoietic stem and progenitors (HSPCs) in BM and subsequently stimulate them to rebuild and sustain the hemato-lymphatic system. However, accumulating evidence now indicates that primitive HSPCs, as well as microenvironmental cells in BM are also able to sense systemically migrating hematopoietic stress signals, and respond by orchestrating on-site hematopoiesis via direct and indirect mechanisms. While inflammation has many beneficial roles in activating the immune system for defense or facilitating tissue repair, it also shows detrimental effects if sustained chronically, i.e., might lead to HSPC damage as bone marrow failure or leukemia. Thus, inflammation requires tight control of initiation and termination in time and space dependent manner.
Literature
1.
Fliedner TM, Graessle D, Paulsen C, Reimers K. Structure and function of bone marrow hemopoiesis: mechanisms of response to ionizing radiation exposure. Cancer Biother Radiopharm. 2002;17:405–26.CrossRefPubMed
2.
Morrison SJ, Wandycz AM, Hemmati HD, Wright DE, Weissman IL. Identification of a lineage of multipotent hematopoietic progenitors. Development. 1997;124:1929–39.PubMed
3.
Pietras EM, Reynaud D, Kang Y-A, Carlin D, Calero-Nieto FJ, Leavitt AD, et al. Functionally distinct subsets of lineage-biased multipotent progenitors control blood production in normal and regenerative conditions. Cell Stem Cell. 2015;17:35–46.CrossRefPubMedPubMedCentral
4.
Laslo P, Spooner CJ, Warmflash A, Lancki DW, Lee H-J, Sciammas R, et al. Multilineage transcriptional priming and determination of alternate hematopoietic cell fates. Cell. 2006;126:755–66.CrossRefPubMed
5.
Adolfsson J, Borge OJ, Bryder D, Theilgaard-Mönch K, Astrand-Grundström I, Sitnicka E, et al. Upregulation of Flt3 expression within the bone marrow Lin(−)Sca1(+)c-kit(+) stem cell compartment is accompanied by loss of self-renewal capacity. Immunity. 2001;15:659–69.CrossRefPubMed
6.
Cabezas-Wallscheid N, Klimmeck D, Hansson J, Lipka DB, Reyes A, Wang Q, et al. Identification of regulatory networks in HSCs and their immediate progeny via integrated proteome, transcriptome, and DNA methylome analysis. Cell Stem Cell. 2014;15:507–22.CrossRefPubMed
7.
Olsson A, Venkatasubramanian M, Chaudhri VK, Aronow BJ, Salomonis N, Singh H, et al. Single-cell analysis of mixed-lineage states leading to a binary cell fate choice. Nature. 2016;537:698–702.CrossRefPubMedPubMedCentral
8.
Paul F, Arkin Y, Giladi A, Jaitin DA, Kenigsberg E, Keren-Shaul H, et al. Transcriptional heterogeneity and lineage commitment in myeloid progenitors. Cell. 2015;163:1663–77.CrossRefPubMed
9.
Rieger MA, Hoppe PS, Smejkal BM, Eitelhuber AC, Schroeder T. Hematopoietic cytokines can instruct lineage choice. Science (New York, N.Y.). 2009;325:217–8.CrossRef
10.
Hoppe PS, Schwarzfischer M, Loeffler D, Kokkaliaris KD, Hilsenbeck O, Moritz N, et al. Early myeloid lineage choice is not initiated by random PU.1 to GATA1 protein ratios. Nature. 2016;535:299–302.CrossRefPubMed
11.
Schofield R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells. 1978;4:7–25.PubMed
12.
Nakamura-Ishizu A, Takizawa H, Suda T. The analysis, roles and regulation of quiescence in hematopoietic stem cells. Development. 2014;141:4656–66.CrossRefPubMed
13.
14.
Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, et al. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003;425:841–6.CrossRefPubMed
15.
Zhang J, Niu C, Ye L, Huang H, He X, Tong W-G, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature. 2003;425:836–41.CrossRefPubMed
16.
17.
Sugiyama T, Kohara H, Noda M, Nagasawa T. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity. 2006;25:977–88.CrossRefPubMed
18.
Takizawa H, Manz MG. In vivo divisional tracking of hematopoietic stem cells. Ann N Y Acad Sci. 2012;1266:40–6.CrossRefPubMed
19.
20.
Busch K, Klapproth K, Barile M, Flossdorf M, Holland-Letz T, Schlenner SM, et al. Fundamental properties of unperturbed haematopoiesis from stem cells in vivo. Nature. 2015;518:542–6.CrossRefPubMed
21.
Sawai CM, Babovic S, Upadhaya S, Knapp DJHF, Lavin Y, Lau CM, et al. Hematopoietic stem cells are the major source of multilineage hematopoiesis in adult animals. Immunity. 2016;45:597–609.CrossRefPubMed
22.
Takizawa H, Boettcher S, Manz MG. Demand-adapted regulation of early hematopoiesis in infection and inflammation. Blood. 2012;119:2991–3002.CrossRefPubMed
23.
Baldridge MT, King KY, Boles NC, Weksberg DC, Goodell MA. Quiescent haematopoietic stem cells are activated by IFN-γ in response to chronic infection. Nature. 2010;465:793–7.CrossRefPubMedPubMedCentral
24.
Burberry A, Zeng MY, Ding L, Wicks I, Inohara N, Morrison SJ, et al. Infection mobilizes hematopoietic stem cells through cooperative NOD-like receptor and toll-like receptor signaling. Cell Host Microbe. 2014;15:779–91.CrossRefPubMedPubMedCentral
25.
Essers MAG, Offner S, Blanco-Bose WE, Waibler Z, Kalinke U, Duchosal MA, et al. IFNα activates dormant haematopoietic stem cells in vivo. Nature. 2009;458:904–8.CrossRefPubMed
26.
Sato T, Onai N, Yoshihara H, Arai F, Suda T, Ohteki T. Interferon regulatory factor-2 protects quiescent hematopoietic stem cells from type I interferon–dependent exhaustion. Nat Med. 2009;15:696–700.CrossRefPubMed
27.
28.
Schmid MA, Takizawa H, Baumjohann DR, Saito Y, Manz MG. Bone marrow dendritic cell progenitors sense pathogens via Toll-like receptors and subsequently migrate to inflamed lymph nodes. Blood. 2011;118:4829–40.CrossRefPubMed
29.
Massberg S, Schaerli P, Knezevic-Maramica I, Köllnberger M, Tubo N, Moseman EA, et al. Immunosurveillance by hematopoietic progenitor cells trafficking through blood, lymph, and peripheral tissues. Cell. 2007;131:994–1008.CrossRefPubMedPubMedCentral
30.
Nagai Y, Garrett KP, Ohta S, Bahrun U, Kouro T, Akira S, et al. Toll-like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment. Immunity. 2006;24:801–12.CrossRefPubMedPubMedCentral
31.
Liu A, Wang Y, Ding Y, Baez I, Payne KJ, Borghesi L. Cutting edge: hematopoietic stem cell expansion and common lymphoid progenitor depletion require hematopoietic-derived, cell-autonomous TLR4 in a model of chronic endotoxin. J Immunol (Baltimore, Md.: 1950). 2015;195:2524–8.CrossRef
32.
Megías J, Yáñez A, Moriano S, O’Connor J-E, Gozalbo D, Gil M-L. Direct toll-like receptor-mediated stimulation of hematopoietic stem and progenitor cells occurs in vivo and promotes differentiation toward macrophages. Stem Cells. 2012;30:1486–95.CrossRefPubMed
33.
34.
Baldridge MT, King KY, Boles NC, Weksberg DC, Goodell MA. Quiescent haematopoietic stem cells are activated by IFN-gamma in response to chronic infection. Nature. 2010;465:793–7.CrossRefPubMedPubMedCentral
35.
Walter D, Lier A, Geiselhart A, Thalheimer FB, Huntscha S, Sobotta MC, et al. Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells. Nature. 2015;520:549–52.CrossRefPubMed
36.
37.
Kitagawa M, Saito I, Kuwata T, Yoshida S, Yamaguchi S, Takahashi M, et al. Overexpression of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma by bone marrow cells from patients with myelodysplastic syndromes. Leukemia. 1997;11:2049–54.CrossRefPubMed
38.
Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, et al. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell. 2008;2:141–50.CrossRefPubMed
39.
Xie Z, Hao H, Tong C, Cheng Y, Liu J, Pang Y, et al. Human umbilical cord-derived mesenchymal stem cells elicit macrophages into an anti-inflammatory phenotype to alleviate insulin resistance in type 2 diabetic rats. Stem Cells. 2016;34:627–39.CrossRefPubMed
40.
Day RB, Bhattacharya D, Nagasawa T, Link DC. Granulocyte colony-stimulating factor reprograms bone marrow stromal cells to actively suppress B lymphopoiesis in mice. Blood. 2015;125:3114–7.CrossRefPubMedPubMedCentral
41.
Schajnovitz A, Itkin T, D’Uva G, Kalinkovich A, Golan K, Ludin A, et al. CXCL12 secretion by bone marrow stromal cells is dependent on cell contact and mediated by connexin-43 and connexin-45 gap junctions. Nat Immunol. 2011;12:391–8.CrossRefPubMed
42.
43.
Martino MM, Maruyama K, Kuhn GA, Satoh T, Takeuchi O, Müller R, et al. Inhibition of IL-1R1/MyD88 signalling promotes mesenchymal stem cell-driven tissue regeneration. Nat Commun. 2016;7:11051.CrossRefPubMedPubMedCentral
44.
45.
Shi C, Jia T, Méndez-Ferrer S, Hohl TM, Serbina NV, Lipuma L, et al. Bone marrow mesenchymal stem and progenitor cells induce monocyte emigration in response to circulating toll-like receptor ligands. Immunity. 2011;34:590–601.CrossRefPubMedPubMedCentral
46.
Wang J, Sun Q, Morita Y, Jiang H, Groß A, Lechel A, et al. A differentiation checkpoint limits hematopoietic stem cell self-renewal in response to DNA damage. Cell. 2012;148:1001–14.CrossRefPubMed
47.
Boettcher S, Ziegler P, Schmid MA, Takizawa H, van Rooijen N, Kopf M, et al. Cutting edge: lPS-induced emergency myelopoiesis depends on TLR4-expressing nonhematopoietic cells. J Immunol. 2012;188:5824–8.CrossRefPubMed
48.
Boettcher S, Gerosa RC, Radpour R, Bauer J, Ampenberger F, Heikenwalder M, et al. Endothelial cells translate pathogen signals into G-CSF-driven emergency granulopoiesis. Blood. 2014;124:1393–403.CrossRefPubMedPubMedCentral
49.
Andonegui G, Zhou H, Bullard D, Kelly MM, Mullaly SC, McDonald B, Long EM, Robbins SM, Kubes P. Mice that exclusively express TLR4 on endothelial cells can efficiently clear a lethal systemic Gram-negative bacterial infection. J Clin Invest. 2009;119(7):1921–30PubMedPubMedCentral
50.
Broudy VC, Kaushansky K, Segal GM, Harlan JM, Adamson JW. Tumor necrosis factor type alpha stimulates human endothelial cells to produce granulocyte/macrophage colony-stimulating factor. Proc Natl Acad Sci USA. 1986;83:7467–71.CrossRefPubMedPubMedCentral
51.
Sieff CA, Tsai S, Faller DV. Interleukin 1 induces cultured human endothelial cell production of granulocyte-macrophage colony-stimulating factor. J Clin Investig. 1987;79:48–51.CrossRefPubMedPubMedCentral
52.
Fernandez L, Rodriguez S, Huang H, Chora A, Fernandes J, Mumaw C, et al. Tumor necrosis factor-α and endothelial cells modulate Notch signaling in the bone marrow microenvironment during inflammation. Exp Hematol. 2008;36:545–58.e1.CrossRefPubMedPubMedCentral
53.
Luu NT, McGettrick HM, Buckley CD, Newsome PN, Rainger GE, Frampton J, et al. Crosstalk between mesenchymal stem cells and endothelial cells leads to downregulation of cytokine-induced leukocyte recruitment. Stem Cells (Dayton, Ohio). 2013;31:2690–702.CrossRef
54.
55.
Ben-Neriah Y, Karin M. Inflammation meets cancer, with NF-κB as the matchmaker. Nat Immunol. 2011;12:715–23.CrossRefPubMed
56.
Kristinsson SY, Landgren O, Samuelsson J, Bjorkholm M, Goldin LR. Autoimmunity and the risk of myeloproliferative neoplasms. Haematologica. 2010;95:1216–20.CrossRefPubMedPubMedCentral
57.
Kristinsson SY, Bjorkholm M, Hultcrantz M, Derolf AR, Landgren O, Goldin LR. Chronic immune stimulation might act as a trigger for the development of acute myeloid leukemia or myelodysplastic syndromes. J Clin Oncol. 2011;29:2897–903.CrossRefPubMedPubMedCentral
58.
Raaijmakers MHGP. Niche contributions to oncogenesis: emerging concepts and implications for the hematopoietic system. Haematologica. 2011;96:1041–8.CrossRefPubMedPubMedCentral
59.
Raaijmakers MHGP, Mukherjee S, Guo S, Zhang S, Kobayashi T, Schoonmaker JA, et al. Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature. 2010;464:852–7.CrossRefPubMedPubMedCentral
60.
Zambetti NA, Ping Z, Chen S, Kenswil KJG, Mylona MA, Sanders MA, et al. Mesenchymal inflammation drives genotoxic stress in hematopoietic stem cells and predicts disease evolution in human pre-leukemia. Cell Stem Cell. 2016;19:613–27.CrossRefPubMed
61.
Takizawa H, Boettcher S, Manz MG. Demand-adapted regulation of early hematopoiesis in infection and inflammation. Blood. 2012;119:2991–3002.CrossRefPubMed
62.
Haas S, Hansson J, Klimmeck D, Loeffler D, Velten L, Uckelmann H, et al. Inflammation-induced emergency megakaryopoiesis driven by hematopoietic stem cell-like megakaryocyte progenitors. Cell Stem Cell. 2015;17:422–34.CrossRefPubMed
63.
Kovtonyuk LV, Fritsch K, Feng X, Manz MG, Takizawa H. Inflamm-aging of hematopoiesis, hematopoietic stem cells, and the bone marrow microenvironment. Front Immunol. 2016;7:502.CrossRefPubMedPubMedCentral
Metadata
Title
Impact of inflammation on early hematopoiesis and the microenvironment
Authors
Hitoshi Takizawa
Markus G. Manz
Publication date
01-07-2017
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 1/2017
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-017-2266-5

Other articles of this Issue 1/2017

International Journal of Hematology 1/2017 Go to the issue

Original Article

Characteristics features and factors influencing early death in Acute promyelocytic leukemia; Experience from United Arab Emirates (UAE)

Original Article

CD4+ memory T cells retain surface expression of CD31 independently of thymic function in patients with lymphoproliferative disorders following autologous hematopoietic stem-cell transplantation

Rapid Communication

Purification of leukemic blast cells from blood smears using laser microdissection

Progress in Hematology

Epigenetic dysregulation of hematopoietic stem cells and preleukemic state

Progress in Hematology

Guest editorial: Hematopoietic stem cells

Progress in Hematology

Complexity of bone marrow hematopoietic stem cell niche
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits