Document Detail

Deletion of tristetraprolin caused spontaneous reactive granulopoiesis by a non-cell-autonomous mechanism without disturbing long-term hematopoietic stem cell quiescence.
MedLine Citation:
PMID:  21270394     Owner:  NLM     Status:  MEDLINE    
Tristetraprolin (TTP, Zfp36, Nup475, Tis11) dramatically reduces the stability of target mRNAs by binding to AU-rich elements in their 3' untranslated regions. Through this mechanism, TTP functions as a rheostatic, temporal regulator of gene expression. TTP knockout (KO) mice exhibit completely penetrant granulocytic hyperplasia. We have shown that the hematopoietic stem-progenitor cell compartment in TTP KO mice is also altered. Although no change was detected in long-term hematopoietic stem cell (HSC) frequency or function, as assayed by immunophenotypic markers or limiting dilution transplants, we observed increases in the frequencies and numbers of short-term HSCs, multipotent progenitors, and granulocyte-monocyte progenitors. This pattern is consistent with "reactive granulopoiesis," in which committed myeloid progenitors and more primitive progenitors cycle more actively to increase production of mature granulocytes in response to infection or adjuvant. We created reverse chimeras by transplanting wild-type bone marrow into TTP KO mice and found the "reactive granulopoiesis" phenocopied, indicating a non-hematopoietic stem-progenitor cell-autonomous mechanism. Correspondingly, we found elevated levels of the granulopoietic TTP targets IL-1β, TNF-α, and IL-6 in the plasma of TTP KO mice. Consistent with the non-cell-autonomous nature of the phenotype, we found elevated levels of IL-1β, TNF-α, and IL-6 transcripts in the livers of TTP KO mice and no detectable difference in the bone marrows. These findings demonstrate the importance of TTP in inflammatory homeostasis and highlight the ability of the hematopoietic system to respond to stress without significant numbers of quiescent HSCs entering the cell cycle.
Ian M Kaplan; Sebastien Morisot; Diane Heiser; Wen-Chih Cheng; Min Jung Kim; Curt I Civin
Related Documents :
21536804 - B cell maturation antigen deficiency exacerbates lymphoproliferation and autoimmunity i...
2572284 - T-cell ontogeny after autologous bone marrow transplantation: failure to synthesize int...
21076044 - Pharmacologic modulation of the calcium-sensing receptor enhances hematopoietic stem ce...
21281644 - A rapid method for assessment of natural killer cell function after multiple receptor c...
3057504 - Human granulocyte-macrophage colony-stimulating factor is a growth factor active on a v...
19372244 - Induction of type 2 t helper cell allergen tolerance by il-10-differentiated regulatory...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-01-26
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  186     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-17     Completed Date:  2011-05-16     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2826-34     Citation Subset:  AIM; IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Bone Marrow Cells / cytology,  immunology,  metabolism
Cell Cycle / immunology
Cells, Cultured
Cytokines / biosynthesis,  metabolism
G0 Phase / genetics,  immunology*
Granulocytes / immunology*,  metabolism,  pathology
Hematopoietic Stem Cells / cytology,  immunology*,  metabolism
Homeostasis / genetics,  immunology
Leukopoiesis / genetics,  immunology*
Liver / immunology,  metabolism,  pathology
Mice, Inbred C57BL
Mice, Knockout
Tristetraprolin / deficiency*,  genetics*,  physiology
Up-Regulation / immunology
Grant Support
P01 CA070970/CA/NCI NIH HHS; P01 CA070970-02/CA/NCI NIH HHS; P01CA070970/CA/NCI NIH HHS
Reg. No./Substance:
0/Cytokines; 0/Tristetraprolin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  The dual functions of IL-1 receptor-associated kinase 2 in TLR9-mediated IFN and proinflammatory cyt...
Next Document:  2B4 Engagement Mediates Rapid LFA-1 and Actin-Dependent NK Cell Adhesion to Tumor Cells as Measured ...