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Reticular Fibroblasts Expressing the Transcription Factor WT1 Define a Stromal Niche that Maintains and Replenishes Splenic Red Pulp Macrophages.
- Source :
-
Immunity [Immunity] 2020 Jul 14; Vol. 53 (1), pp. 127-142.e7. Date of Electronic Publication: 2020 Jun 19. - Publication Year :
- 2020
-
Abstract
- Located within red pulp cords, splenic red pulp macrophages (RPMs) are constantly exposed to the blood flow, clearing senescent red blood cells (RBCs) and recycling iron from hemoglobin. Here, we studied the mechanisms underlying RPM homeostasis, focusing on the involvement of stromal cells as these cells perform anchoring and nurturing macrophage niche functions in lymph nodes and liver. Microscopy revealed that RPMs are embedded in a reticular meshwork of red pulp fibroblasts characterized by the expression of the transcription factor Wilms' Tumor 1 (WT1) and colony stimulating factor 1 (CSF1). Conditional deletion of Csf1 in WT1 <superscript>+</superscript> red pulp fibroblasts, but not white pulp fibroblasts, drastically altered the RPM network without altering circulating CSF1 levels. Upon RPM depletion, red pulp fibroblasts transiently produced the monocyte chemoattractants CCL2 and CCL7, thereby contributing to the replenishment of the RPM network. Thus, red pulp fibroblasts anchor and nurture RPM, a function likely conserved in humans.<br />Competing Interests: Declaration of Interests The authors declare no competing interests<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Chemokine CCL2 metabolism
Chemokine CCL7 metabolism
Gene Expression Regulation
Humans
Immunity, Innate immunology
Iron metabolism
Macrophage Colony-Stimulating Factor genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Monocytes immunology
Rats
Signal Transduction immunology
Spleen metabolism
Fibroblasts metabolism
Macrophage Colony-Stimulating Factor metabolism
Macrophages immunology
Spleen cytology
WT1 Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4180
- Volume :
- 53
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Immunity
- Publication Type :
- Academic Journal
- Accession number :
- 32562599
- Full Text :
- https://doi.org/10.1016/j.immuni.2020.06.008