Details

Autor(en) / Beteiligte

• Gerosa, Rahel C.
• Boettcher, Steffen
• Kovtonyuk, Larisa V.
• Hausmann, Annika
• Hardt, Wolf-Dietrich
• Hidalgo, Juan
• Nombela-Arrieta, César
• Manz, Markus G.

Titel

CXCL12-abundant reticular cells are the major source of IL-6 upon LPS stimulation and thereby regulate hematopoiesis

Ist Teil von

• Blood advances, 2021-12, Vol.5 (23), p.5002-5015

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. •BM CAR cells are the major source of local and systemic IL-6 levels upon LPS-induced inflammation.•BM CAR cell–derived IL-6 is critical to sustain an adequate hematopoietic response during chronic repetitive LPS-induced inflammation. [Display omitted]