Journal
JOURNAL OF IMMUNOLOGY
Volume 195, Issue 6, Pages 2524-2528Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1501231
Keywords
-
Categories
Funding
- National Institutes of Health [AI079047, AI105846, P20 MD006988, P30 CA4790413]
- American Society of Hematology Bridge Grant Program
- Department of Pathology and Human Anatomy
- Department of Basic Sciences
- Center for Health Disparities and Molecular Medicine
- Hillman Cancer Center support grant
Ask authors/readers for more resources
Hematopoietic stem and progenitors cells (HSPCs) are activated through TLR4 in vitro. However, it remains unclear whether in vivo TLR4 sensing by HSPCs occurs directly or via other cell intermediates. In this study, we examined the cellular mechanisms underlying murine hematopoietic stem cell (HSC) expansion and common lymphoid progenitor (CLP) depletion in a model of chronic low-dose LPS. Using adoptive-transfer approaches, we show that HSC and CLP sensitivity to chronic LPS depends on hematopoietic-derived, cell subset-autonomous TLR4. Like murine progenitors, human HSPCs are activated by TLR4 in vitro. Using humanized mice, a preclinical model relevant to human physiology, we show that persistent endotoxin increases the frequency of Ki-67(+) HSCs and severely depletes CLPs and B precursors. Together, our findings show that murine HSPCs directly respond to endotoxin in vivo and that persistent LPS, a feature of several diseases of global health significance, impairs human lymphopoiesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available