Stress-associated erythropoiesis initiation is regulated by type 1 conventional dendritic cells
Taeg S. Kim, … , Paul C. Trampont, Thomas J. Braciale
Taeg S. Kim, … , Paul C. Trampont, Thomas J. Braciale
Published September 21, 2015
Citation Information: J Clin Invest. 2015;125(10):3965-3980. https://doi.org/10.1172/JCI81919.
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Research Article Immunology

Stress-associated erythropoiesis initiation is regulated by type 1 conventional dendritic cells

Abstract

Erythropoiesis is an important response to certain types of stress, including hypoxia, hemorrhage, bone marrow suppression, and anemia, that result in inadequate tissue oxygenation. This stress-induced erythropoiesis is distinct from basal red blood cell generation; however, neither the cellular nor the molecular factors that regulate this process are fully understood. Here, we report that type 1 conventional dendritic cells (cDC1s), which are defined by expression of CD8α in the mouse and XCR1 and CLEC9 in humans, are critical for induction of erythropoiesis in response to stress. Specifically, using murine models, we determined that engagement of a stress sensor, CD24, on cDC1s upregulates expression of the Kit ligand stem cell factor on these cells. The increased expression of stem cell factor resulted in Kit-mediated proliferative expansion of early erythroid progenitors and, ultimately, transient reticulocytosis in the circulation. Moreover, this stress response was triggered in part by alarmin recognition and was blunted in CD24 sensor– and CD8α+ DC-deficient animals. The contribution of the cDC1 subset to the initiation of stress erythropoiesis was distinct from the well-recognized role of macrophages in supporting late erythroid maturation. Together, these findings offer insight into the mechanism of stress erythropoiesis and into disorders of erythrocyte generation associated with stress.

Authors

Taeg S. Kim, Mark Hanak, Paul C. Trampont, Thomas J. Braciale

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Figure 7

Splenic CD8α+ DCs are a major source for SCF produced after CD24 engagement.

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Splenic CD8α+ DCs are a major source for SCF produced after CD24 engagem...
(A) Single-cell suspensions prepared from spleens of naive mice were incubated with control Ig or M1/69 for 12 hours in vitro and examined for mSCF expressed by splenic DC subsets. (B) WT B6 mice treated with M1/69 in vivo were harvested at 12 hours after Ab treatment. Splenic DC subsets were examined for the expression of mSCF. Data shown in A and B represent at least 3 independent experiments. (C) At various times after M1/69 treatment, the indicated organs were harvested, and mSCF mRNA expression levels were examined. Data represent mean ± SEM (n = 3–5). (D) WT B6 mice were treated i.p. with M1/69. At 12 hours after Ab treatment, the indicated cell types in the spleen were individually FACS sorted. Expression of Scf mRNAs was examined and presented as fold change compared with those from Ig-treated mice (pooled from 4 mice/sorting). Data represent 2 independent experiments. (E) WT and Batf3–/– mice were treated i.p. with M1/69. Spleens were harvested at 12 hours after Ab treatment. Scf mRNA expression levels were measured. Data represent mean ± SEM (n = 3–5/genotype).