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TLR agonists induce the differentiation of human bone marrow CD34+ progenitors into CD11c+ CD80/86+ DC capable of inducing a Th1-type response.
Eur J Immunol. 2007 Oct; 37(10):2834-46.EJ

Abstract

We recently reported that human bone marrow hematopoietic CD34(+) progenitors express functional Toll-like receptors (TLR) and can differentiate into myeloid cells just by stimulation with resiquimod (R848), a specific agonist for TLR7/8. However, the mechanisms by which R848 induces cell differentiation, the effects of other TLR agonists and the functionality of the differentiated cells are not known. Comparable to R848, loxoribine (a TLR7 agonist) and Pam(3)CSK(4) (a TLR2 agonist) induced cytokine production and cell differentiation along the myeloid lineage. R848 and loxoribine were more effective than Pam(3)CSK(4) at inducing the lineage-negative (CD11c(+) CD14(-)) dendritic cells (DC), whereas Pam(3)CSK(4) was more effective at inducing CD11c(+) CD14(+) monocytes. Both cell subsets expressed CD80/CD86 and HLA-DR molecules; however, they showed differential expression of CD1a, CD1b, CD1c, CD11b, CD206 and CD207 markers when compared with each other. Cell differentiation into DC was significantly inhibited by an anti-TNF-alpha nonoclonal antibody. The CD11c(+) CD14(-) subset was isolated and shown to be more potent in stimulating an alloreaction than the CD11c(+) CD14(+) subset. Collectively, these data highlight the differential effects of TLR agonists on human bone marow CD34(+) progenitor cells and provide a new opportunity for generating functional DC that would be useful in cancer vaccination.

Authors+Show Affiliations

Department of Immunology, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway. mosioud@ulrik.uio.noNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17853407

Citation

Sioud, Mouldy, and Yngvar Fløisand. "TLR Agonists Induce the Differentiation of Human Bone Marrow CD34+ Progenitors Into CD11c+ CD80/86+ DC Capable of Inducing a Th1-type Response." European Journal of Immunology, vol. 37, no. 10, 2007, pp. 2834-46.
Sioud M, Fløisand Y. TLR agonists induce the differentiation of human bone marrow CD34+ progenitors into CD11c+ CD80/86+ DC capable of inducing a Th1-type response. Eur J Immunol. 2007;37(10):2834-46.
Sioud, M., & Fløisand, Y. (2007). TLR agonists induce the differentiation of human bone marrow CD34+ progenitors into CD11c+ CD80/86+ DC capable of inducing a Th1-type response. European Journal of Immunology, 37(10), 2834-46.
Sioud M, Fløisand Y. TLR Agonists Induce the Differentiation of Human Bone Marrow CD34+ Progenitors Into CD11c+ CD80/86+ DC Capable of Inducing a Th1-type Response. Eur J Immunol. 2007;37(10):2834-46. PubMed PMID: 17853407.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TLR agonists induce the differentiation of human bone marrow CD34+ progenitors into CD11c+ CD80/86+ DC capable of inducing a Th1-type response. AU - Sioud,Mouldy, AU - Fløisand,Yngvar, PY - 2007/9/14/pubmed PY - 2007/12/6/medline PY - 2007/9/14/entrez SP - 2834 EP - 46 JF - European journal of immunology JO - Eur J Immunol VL - 37 IS - 10 N2 - We recently reported that human bone marrow hematopoietic CD34(+) progenitors express functional Toll-like receptors (TLR) and can differentiate into myeloid cells just by stimulation with resiquimod (R848), a specific agonist for TLR7/8. However, the mechanisms by which R848 induces cell differentiation, the effects of other TLR agonists and the functionality of the differentiated cells are not known. Comparable to R848, loxoribine (a TLR7 agonist) and Pam(3)CSK(4) (a TLR2 agonist) induced cytokine production and cell differentiation along the myeloid lineage. R848 and loxoribine were more effective than Pam(3)CSK(4) at inducing the lineage-negative (CD11c(+) CD14(-)) dendritic cells (DC), whereas Pam(3)CSK(4) was more effective at inducing CD11c(+) CD14(+) monocytes. Both cell subsets expressed CD80/CD86 and HLA-DR molecules; however, they showed differential expression of CD1a, CD1b, CD1c, CD11b, CD206 and CD207 markers when compared with each other. Cell differentiation into DC was significantly inhibited by an anti-TNF-alpha nonoclonal antibody. The CD11c(+) CD14(-) subset was isolated and shown to be more potent in stimulating an alloreaction than the CD11c(+) CD14(+) subset. Collectively, these data highlight the differential effects of TLR agonists on human bone marow CD34(+) progenitor cells and provide a new opportunity for generating functional DC that would be useful in cancer vaccination. SN - 0014-2980 UR - https://www.unboundmedicine.com/medline/citation/17853407/TLR_agonists_induce_the_differentiation_of_human_bone_marrow_CD34+_progenitors_into_CD11c+_CD80/86+_DC_capable_of_inducing_a_Th1_type_response_ L2 - https://doi.org/10.1002/eji.200737112 DB - PRIME DP - Unbound Medicine ER -