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The concerted action of GM-CSF and Flt3-ligand on in vivo dendritic cell homeostasis


Kingston, D; Schmid, M A; Onai, N; Obata-Onai, A; Baumjohann, D; Manz, M G (2009). The concerted action of GM-CSF and Flt3-ligand on in vivo dendritic cell homeostasis. Blood, 114(4):835-843.

Abstract

Dendritic cell (DC) development is efficiently supported by Flt3-ligand or GM-CSF in vitro, and lymphoid-organ DC maintenance in vivo is critically dependent on Flt3-ligand. However, the relevance of GM-CSF for lymphoid-tissue DC maintenance and the importance of both cytokines for nonlymphoid organ DC homeostasis are not defined. Here, we show that, although Gm-csfr and Flt3 are both expressed in DC progenitors, Gm-csfr is expressed predominantly in monocytes, classical DCs (cDCs), and skin DCs, whereas Flt3 is expressed in both cDCs and plasmacytoid DCs (pDCs). In accordance with the respective cytokine receptor expression, DC progenitor and pDC numbers are primarily affected by Flt3-ligand deficiency, whereas both splenic and lymph node cDCs and dermal DCs are reduced in the absence of either GM-CSF or Flt3-ligand. Combined lack of GM-CSF and Flt3-ligand in newly generated double-deficient mice leads to further significant reductions of DC progenitors and dermal DCs. In line with the decrease of respective DC subsets, T-cell and antigen-specific IgG responses decline progressively, from wild-type to GM-CSF- to Flt3-ligand- to double-deficient mice, upon subcutaneous antigen delivery. These data thus show the concerted action of GM-CSF and Flt3-ligand on DC homeostasis in vivo.

Dendritic cell (DC) development is efficiently supported by Flt3-ligand or GM-CSF in vitro, and lymphoid-organ DC maintenance in vivo is critically dependent on Flt3-ligand. However, the relevance of GM-CSF for lymphoid-tissue DC maintenance and the importance of both cytokines for nonlymphoid organ DC homeostasis are not defined. Here, we show that, although Gm-csfr and Flt3 are both expressed in DC progenitors, Gm-csfr is expressed predominantly in monocytes, classical DCs (cDCs), and skin DCs, whereas Flt3 is expressed in both cDCs and plasmacytoid DCs (pDCs). In accordance with the respective cytokine receptor expression, DC progenitor and pDC numbers are primarily affected by Flt3-ligand deficiency, whereas both splenic and lymph node cDCs and dermal DCs are reduced in the absence of either GM-CSF or Flt3-ligand. Combined lack of GM-CSF and Flt3-ligand in newly generated double-deficient mice leads to further significant reductions of DC progenitors and dermal DCs. In line with the decrease of respective DC subsets, T-cell and antigen-specific IgG responses decline progressively, from wild-type to GM-CSF- to Flt3-ligand- to double-deficient mice, upon subcutaneous antigen delivery. These data thus show the concerted action of GM-CSF and Flt3-ligand on DC homeostasis in vivo.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Hematology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:23 July 2009
Deposited On:15 Feb 2010 14:09
Last Modified:05 Apr 2016 13:51
Publisher:American Society of Hematology
ISSN:0006-4971
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:10.1182/blood-2009-02-206318
PubMed ID:19465690

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