CXCL12-abundant reticular cells are the major source of IL-6 upon LPS stimulation and thereby regulate hematopoiesis
Gerosa, Rahel C. (University of Zurich)
Boettcher, Steffen (University of Zurich)
Kovtonyuk, Larisa V. (University Hospital Zurich (Suïssa))
Hausmann, Annika (The Institute of Microbiology)
Hardt, Wolf-Dietrich (The Institute of Microbiology)
Hidalgo Pareja, Juan (Universitat Autònoma de Barcelona. Institut de Neurociències)
Nombela-Arrieta, César (University of Zurich)
Manz, Markus G. (University of Zurich)

Fecha:	2021
Resumen:	Hematopoiesis is maintained by hematopoietic stem and progenitor cells that are located in the bone marrow (BM) where they are embedded within a complex supportive microenvironment consisting of a multitude of various non-hematopoietic and hematopoietic cell types. The BM microenvironment not only regulates steady-state hematopoiesis by provision of growth factors, cytokines, and cell-cell contact but is also an emerging key player during the adaptation to infectious and inflammatory insults (emergency hematopoiesis). Through a combination of gene expression analyses in prospectively isolated non-hematopoietic BM cell populations and various mouse models, we found that BM CXCL12-abundant reticular (CAR) cells are a major source of systemic and local BM interleukin-6 (IL-6) levels during emergency hematopoiesis after lipopolysaccharide (LPS) stimulation. Importantly, although IL-6 is dispensable during the initial phase of LPS-induced emergency hematopoiesis, it is required to sustain an adequate hematopoietic output during chronic repetitive inflammation. Our data highlight the essential role of the non-hematopoietic BM microenvironment for the sensing and integration of pathogen-derived signals into sustained demand-adapted hematopoietic responses.
Ayudas:	Ministerio de Economía y Competitividad SAF2014-56546-R Agencia Estatal de Investigación RTI2018-101105-B-I00
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Blood advances, Vol. 5 (december 2021) , p. 5002-5015, ISSN 2473-9537

DOI: 10.1182/bloodadvances.2021005531
PMID: 34581809

14 p, 2.5 MB

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