Altered compensatory cytokine signaling underlies the discrepancy between Flt3-/- and Flt3l-/- mice.
J Exp Med
; 215(5): 1417-1435, 2018 05 07.
Article
in En
| MEDLINE
| ID: mdl-29572360
ABSTRACT
The receptor Flt3 and its ligand Flt3L are both critical for dendritic cell (DC) development, but DC deficiency is more severe in Flt3l-/- mice than in Flt3-/- mice. This has led to speculation that Flt3L binds to another receptor that also supports DC development. However, we found that Flt3L administration does not generate DCs in Flt3-/- mice, arguing against a second receptor. Instead, Flt3-/- DC progenitors matured in response to macrophage colony-stimulating factor (M-CSF) or stem cell factor, and deletion of Csf1r in Flt3-/- mice further reduced DC development, indicating that these cytokines could compensate for Flt3. Surprisingly, Flt3-/- DC progenitors displayed enhanced M-CSF signaling, suggesting that loss of Flt3 increased responsiveness to other cytokines. In agreement, deletion of Flt3 in Flt3l-/- mice paradoxically rescued their severe DC deficiency. Thus, multiple cytokines can support DC development, and the discrepancy between Flt3-/- and Flt3l-/- mice results from the increased sensitivity of Flt3-/- progenitors to these cytokines.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
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Cytokines
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Fms-Like Tyrosine Kinase 3
/
Membrane Proteins
Limits:
Animals
Language:
En
Journal:
J Exp Med
Year:
2018
Document type:
Article
Affiliation country:
Macao
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
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EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
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US
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USA