Distinct contributions of TNF and LT cytokines to the development of dendritic cells in vitro and their recruitment in vivo
| Autor: | Sergei A. Nedospasov, Koichiro Abe, Kristin L. Komschlies, Daisuke Ito, Klaus Pfeffer, Alexei V. Tumanov, Shakhov An, Dmitry V. Kuprash, Takaya Murakami, Ludmila N. Drutskaya, Felix Yarovinsky |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Lymphotoxin-beta
Chemokine medicine.medical_treatment T-Lymphocytes Immunology Gene Expression Bone Marrow Cells Cell Count Lymphotoxin beta Biochemistry Receptors Tumor Necrosis Factor Mice Lymphotoxin beta Receptor medicine Animals Antigen-presenting cell Lymphotoxin-alpha Cells Cultured Mice Knockout Lymphokines biology Tumor Necrosis Factor-alpha Stem Cells Membrane Proteins Cell Biology Hematology Dendritic cell Dendritic Cells Flow Cytometry Molecular biology Recombinant Proteins Cytokine Lymphotoxin biology.protein Tumor necrosis factor alpha Lymphocyte Culture Test Mixed Lymphotoxin beta receptor Spleen |
| Zdroj: | Blood. 101(4) |
| ISSN: | 0006-4971 |
| Popis: | TNF/LTalpha/LTbeta (tumor necrosis factor/lymphotoxin-alpha/lymphotoxin-beta) triple knockout (KO) mice show a significant reduction of dendritic cell (DC) number in the spleen, presumably due to defective recruitment and/or production. To distinguish between these possibilities, DCs were generated from bone marrow (BM) cultures prepared from wild-type (wt) and mutant mice in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). The yield of CD11c(+) major histocompatibility complex (MHC) class II(+) DCs generated from TNF/LTalpha/LTbeta(-/-) BM culture was significantly reduced compared with wt BM culture. In order to further dissect the individual pathways responsible for defective DC properties observed in TNF/LTalpha/LTbeta(-/-) mice, the panel of TNF/LT ligand and receptor single KO mice were used. The production of DCs from BM culture was significantly reduced in TNF(-/-) and TNF receptor (TNFR) p55(-/-) mice, but normal in LTalpha(-/-), LTbeta(-/-), LTbetaR(-/-) mice. Recombinant TNF (rTNF) exogenously added to TNF/LTalpha/LTbeta(-/-) BM cultures could reverse this defect, and blocking antibodies showed partial effect on BM cultures of wt mice. Conversely, numbers of mature DCs in spleen were significantly decreased in LTalpha(-/-), LTbeta(-/-), LTbetaR(-/-) mice, but not in TNF(-/-) and TNFRp55(-/-) mice. These results reveal 2 distinct contributions of TNF/LT cytokines. First, TNF acting through TNF receptor is involved in the development/maturation of DCs in BM progenitor cultures, but this function appears to be redundant in vivo. Second, the microenvironment in peripheral lymphoid organs associated with LTalpha/LTbeta-LTbetaR signaling and chemokine production is critical for recruitment efficiency of DCs, and this pathway is indispensable. |
| Databáze: | OpenAIRE |
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