DOI: 10.1182/blood.v93.4.1208. Transforming Growth Factor-β1 Polarizes Murine Hematopoietic Progenitor Cells to Generate Langerhans Cell-Like Dendritic Cells Through a Monocyte/Macrophage Differentiation Pathway

Transforming Growth Factor-β1 Polarizes Murine Hematopoietic Progenitor Cells to Generate Langerhans Cell-Like Dendritic Cells Through a Monocyte/Macrophage Differentiation Pathway

10.1182/blood.v93.4.1208

Crossref journal-article

American Society of Hematology

Blood (234)

Abstract

AbstractWe have recently demonstrated that CD11b−/dullCD11c+ and CD11b+hiCD11c+ dendritic cell (DC) precursor subsets represent two distinct DC differentiation pathways from murine bone marrow lineage-phenotype negative (Lin−)c-kit+ hematopoietic progenitor cells (HPCs) stimulated with granulocyte-macrophage colony-stimulating factor (GM-CSF) + stem cell factor (SCF) + tumor necrosis factor  (TNF). We show here that transforming growth factor-β1 (TGF-β1) significantly inhibits the generation of these CD11b−/dullCD11c+ and CD11b+hiCD11c+ DC precursors. Phenotypically, this inhibitory effect was accompanied by markedly suppressed expression of Ia and CD86 antigens as well as major histocompatibility complex (MHC) class II transactivator (CIITA) and CC-chemokine receptor 7 (CCR7) mRNAs in Lin−c-kit+ HPC cultures stimulated with GM-CSF + SCF + TNF at day 6. TGF-β1 could also suppress mature DC differentiation from CD11b+hiCD11c+ DC precursors, but not the differentiation from CD11b−/dullCD11c+ DC precursors. In the absence of TNF, TGF-β1 markedly suppressed the expression of CIITA and CCR7 mRNAs in GM-CSF + SCF-stimulated Lin−c-kit+ HPCs at either day 6 or day 12 and induced the differentiation solely into monocytes/macrophages as evident in morphology, active phagocytic, and endocytic activities. These cells expressed high levels of F4/80 and E-cadherin antigens, but low or undetectable levels of Ia, CD86, and CD40 molecules. However, upon the stimulation with TNF + GM-CSF, these cells could further differentiate into mature DCs expressing high levels of Ia and E-cadherin, characteristics for Langerhans cells (LCs), and gained the capacity of enhancing allogenic MLR. Taken together, all of these findings suggest that TGF-β1 polarizes murine HPCs to generate LC-like DCs through a monocyte/macrophage differentiation pathway.

Authors 7

Yi Zhang (first)
Yan-yun Zhang (additional)
Masafumi Ogata (additional)
Pan Chen (additional)
Akihisa Harada (additional)
Shin-ichi Hashimoto (additional)
Kouji Matsushima (additional)

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Dates

Type	When
Created	5 years, 10 months ago (Oct. 14, 2019, 6:36 a.m.)
Deposited	1 year, 11 months ago (Sept. 21, 2023, 12:50 p.m.)
Indexed	11 months, 2 weeks ago (Sept. 12, 2024, 2:35 a.m.)
Issued	26 years, 6 months ago (Feb. 15, 1999)
Published	26 years, 6 months ago (Feb. 15, 1999)
Published Print	26 years, 6 months ago (Feb. 15, 1999)

Funders 0

None

BibTeX

@article{Zhang_1999, title={Transforming Growth Factor-β1 Polarizes Murine Hematopoietic Progenitor Cells to Generate Langerhans Cell-Like Dendritic Cells Through a Monocyte/Macrophage Differentiation Pathway}, volume={93}, ISSN={0006-4971}, url={http://dx.doi.org/10.1182/blood.v93.4.1208}, DOI={10.1182/blood.v93.4.1208}, number={4}, journal={Blood}, publisher={American Society of Hematology}, author={Zhang, Yi and Zhang, Yan-yun and Ogata, Masafumi and Chen, Pan and Harada, Akihisa and Hashimoto, Shin-ichi and Matsushima, Kouji}, year={1999}, month=feb, pages={1208–1220} }

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  "abstract": "<jats:title>Abstract</jats:title><jats:p>We have recently demonstrated that CD11b\u2212/dullCD11c+ and CD11b+hiCD11c+ dendritic cell (DC) precursor subsets represent two distinct DC differentiation pathways from murine bone marrow lineage-phenotype negative (Lin\u2212)c-kit+ hematopoietic progenitor cells (HPCs) stimulated with granulocyte-macrophage colony-stimulating factor (GM-CSF) + stem cell factor (SCF) + tumor necrosis factor \ue700 (TNF\ue700). We show here that transforming growth factor-\u03b21 (TGF-\u03b21) significantly inhibits the generation of these CD11b\u2212/dullCD11c+ and CD11b+hiCD11c+ DC precursors. Phenotypically, this inhibitory effect was accompanied by markedly suppressed expression of Ia and CD86 antigens as well as major histocompatibility complex (MHC) class II transactivator (CIITA) and CC-chemokine receptor 7 (CCR7) mRNAs in Lin\u2212c-kit+ HPC cultures stimulated with GM-CSF + SCF + TNF\ue700 at day 6. TGF-\u03b21 could also suppress mature DC differentiation from CD11b+hiCD11c+ DC precursors, but not the differentiation from CD11b\u2212/dullCD11c+ DC precursors. In the absence of TNF\ue700, TGF-\u03b21 markedly suppressed the expression of CIITA and CCR7 mRNAs in GM-CSF + SCF-stimulated Lin\u2212c-kit+ HPCs at either day 6 or day 12 and induced the differentiation solely into monocytes/macrophages as evident in morphology, active phagocytic, and endocytic activities. These cells expressed high levels of F4/80 and E-cadherin antigens, but low or undetectable levels of Ia, CD86, and CD40 molecules. However, upon the stimulation with TNF\ue700 + GM-CSF, these cells could further differentiate into mature DCs expressing high levels of Ia and E-cadherin, characteristics for Langerhans cells (LCs), and gained the capacity of enhancing allogenic MLR. Taken together, all of these findings suggest that TGF-\u03b21 polarizes murine HPCs to generate LC-like DCs through a monocyte/macrophage differentiation pathway.</jats:p>",
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