Altered Compensatory Cytokine Signaling Underlies the Discrepancy Between and Mice

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2018 Mar 25

PMID 29572360

Citations 28

Authors

Vivek Durai

Prachi Bagadia

Carlos G Briseno

Derek J Theisen

Arifumi Iwata

Jesse T Davidson 4th

Marco Gargaro

Daved H Fremont

Theresa L Murphy

Kenneth M Murphy

Affiliations

Soon will be listed here.

Abstract

The receptor Flt3 and its ligand Flt3L are both critical for dendritic cell (DC) development, but DC deficiency is more severe in mice than in 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 mice, arguing against a second receptor. Instead, DC progenitors matured in response to macrophage colony-stimulating factor (M-CSF) or stem cell factor, and deletion of in mice further reduced DC development, indicating that these cytokines could compensate for Flt3. Surprisingly, DC progenitors displayed enhanced M-CSF signaling, suggesting that loss of Flt3 increased responsiveness to other cytokines. In agreement, deletion of Flt3 in mice paradoxically rescued their severe DC deficiency. Thus, multiple cytokines can support DC development, and the discrepancy between and mice results from the increased sensitivity of progenitors to these cytokines.

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