Monocyte Induction of IL-10 and Down-Regulation of IL-12 by iC3b Deposited in Ultraviolet-Exposed Human Skin
| Autor: | Yoshida Y, Kang K, Berger M, Chen G, Ac, Gilliam, Moser A, Wu L, Hammerberg C, Kevin Cooper |
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| Rok vydání: | 1998 |
| Předmět: | |
| Zdroj: | Europe PubMed Central |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.161.11.5873 |
| Popis: | CD11b+ monocytic/macrophagic cells (Mo/Mph), which infiltrate into skin after UV irradiation, play an important role in UV-induced immunosuppression. Because in mice, blockade of CD11b (iC3b receptor) on monocytes and depletion of its ligand, iC3b, reverses UV-induced immunosuppression, we asked whether iC3b is deposited in human skin after UV, and whether iC3b can modulate the cytokine profile of Mo/Mph. Immunofluorescence studies revealed that iC3b was newly deposited in UV-exposed skin and was localized in apposition to infiltrating CD11b+ Mo/Mph. In addition, in situ hybridization studies showed that TNF-α mRNA was also induced in a similar microanatomic localization. To model the effects of these complex signals on infiltrating Mo/Mph following UV exposure, we then tested the effects of immobilized iC3b and TNF-α on resting blood monocytes. Both IL-10 mRNA synthesis and protein secretion were significantly induced by binding of iC3b in vitro and were synergistically increased by the presence of TNF-α. The effect was abrogated by a blocking Ab to CD11b, indicating CD11b-iC3b interaction. In contrast, iC3b binding resulted in suppression of IL-12 p40 mRNA and significantly inhibited the production of IL-12 p70 protein. Our studies thus define a novel mechanism for induction of tissue Mo/Mph into an IL-10high/IL-12low state via iC3b in combination with TNF-α. |
| Databáze: | OpenAIRE |
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